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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation V30M

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 9 clinical trials

Clinical Trials


1 Safety and Efficacy of Orally Administered Fx-1006A in Patients With Familial Amyloid Polyneuropathy (FAP): A Randomized, Double-blind, Placebo-controlled Study

This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP). Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience. This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.

NCT00409175
Conditions
  1. Familial Amyloid Polyneuropathy
Interventions
  1. Drug: Fx-1006A
  2. Drug: Placebo
MeSH:Polyneuropathies Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis
HPO:Amyloidosis Lattice corneal dystrophy Motor polyneuropathy Polyneuropathy

Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. --- V30M ---

Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months. --- V30M ---

2. Documented V30M TTR mutation. --- V30M ---

Primary Outcomes

Description: Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than[<] 2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

Measure: Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18

Time: Month 18

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

Measure: Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18

Time: Baseline, Month 18

Secondary Outcomes

Description: NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment.

Measure: Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to <2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0 (normal) to 4 (paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

Measure: Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12

Time: Month 6, 12

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

Measure: Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12

Time: Baseline, Month 6, 12

Description: Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7:scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale: 0=no problem, 4=severe problem (except item 32: -2=much better, 0=about same, 2=much worse). Norfolk QOL-DN summarized in 5 domains(score range):physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptoms(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12); higher score=greater impairment, for each. Total score=-2 to138(higher score=worse QOL).

Measure: Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: Summated 7 score: composite score included five Nerve Conduction Studies (NCS) attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with Vibration Detection Threshold (VDT) obtained in great toes, and Heart Rate Response to Deep Breathing (HRDB) value. Score was determined through reference to normal values for age, sex and height. Total score range= -26 to 26, where higher score=worse nerve function.

Measure: Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: Summated 3 Nerve Tests Small Fiber Normal Deviates Score (NTSFnds) included cooling threshold for the lower limbs, heat pain threshold for the lower limbs and HRDB. Total score range= -11.2 to 11.2, where higher score=worse nerve function.

Measure: Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation associated with malnutrition. A progressive decline in mBMI indicated worsening of disease severity.

Measure: Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer

Time: Week 8, Month 6, 12, 18

2 The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis

This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. Strong pre-clinical and clinical evidence support a daily dose of 20 mg of Fx-1006A to be the optimum dose to achieve stabilization of tetrameric TTR in ATTR-PN patients. Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. Safety and exploratory efficacy of Fx-1006A administered once daily for 12 months will also be evaluated in this patient population. This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will receive oral Fx-1006A 20 mg soft gelatin capsules once daily for six weeks. At Week 6, blood samples will be collected from each patient to determine TTR stabilization. Patients who complete the Week 6 visit will continue receiving daily oral Fx-1006A 20 mg for up to a total of 12 months during Part 2 of this study. If it is determined that a patient is not stabilized at Week 6, the patient will be discontinued from the study. During Part 2, clinical outcomes will be measured at Months 6 and 12, based on NIS, Norfolk QOL-DN, mBMI, NCS, HRDB, SF-36, Karnofsky score, and echocardiography; NT-pro-BNP and troponin I levels will be measured at Baseline, Weeks 2 and 6, and Months 3, 6, and 12. Pharmacokinetic measurements will be made using samples collected at Baseline, Week 6, and Months 6 and 12. Safety and tolerability will be assessed throughout the study based on vital signs, physical examinations, ECG, echocardiography, 24-hour Holter monitoring, clinical laboratory tests (hematology, serum chemistry, and urinalysis), and monitoring adverse events and concomitant medication use. Day 1 will be defined as administration of the first dose of study drug. Clinic Visits will be conducted during Screening (Days -30 to -1) and at Baseline (Day 0), and Week 2, and Week 6, and Months 3, 6, and 12 (± 2 weeks of the scheduled date for post-Baseline visits). Monthly telephone contacts (+ 1 week of the scheduled date) will be made during months in which no investigative site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for assessment of adverse events and concomitant medications. A final telephone contact to assess adverse events and concomitant medication usage will be made 30 days after the last dose of study drug. Patients who discontinue from the study at any time following enrollment will have a final visit performed, including all safety assessments, at the time of discontinuation. Any patient discontinuing after the Month 6 visit will also have all exploratory assessments performed.

NCT00630864
Conditions
  1. Transthyretin-associated Amyloidosis With Polyneuropathy
Interventions
  1. Drug: Fx-1006A
MeSH:Polyneuropathies Amyloidosis
HPO:Amyloidosis Motor polyneuropathy Polyneuropathy

The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis. --- V30M ---

The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. --- V30M ---

The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. --- V30M --- --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M --- --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M --- --- V30M --- --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M --- --- V30M --- --- V30M --- --- V30M ---

This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. --- V30M ---

- Patient has TTR-associated amyloidosis with V30M mutation. --- V30M ---

Primary Outcomes

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6

Time: Week 6

Secondary Outcomes

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The FOI is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12

Time: Month 6, Month 12

Other Outcomes

Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)

Time: Baseline up to 30 days after the last dose

Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. On the basis of intensity, grade 3 was referred as severe, grade 4 as life-threatening and grade 5 as death.

Measure: Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events

Time: Baseline up to 30 days after the last dose

Description: ECHO: investigator assessed test to assess cardiac function. ECHO abnormality criteria: any abnormality, valvular abnormality, pericardial effusion, abnormal regional wall motion, inferior vena cava respiratory variation, posterior (P) left ventricular (LV) wall/septal (S) thickness, right ventricular thickness, ejection fraction, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A), ratio of 'E'to lateral/septal mitral annular velocity (e') (E/e'prime lateral, E/e'prime septal), E deceleration time (DT), isovolumic relaxation time (IVRT).

Measure: Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings

Time: Day 1 up to Month 12

Description: ECG: investigator assessed test to assess cardiac function. ECG abnormality criteria: any abnormality, arrhythmia, rhythm, conduction, morphology, myocardial infarction, ST segment, T waves and abnormal U waves.

Measure: Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings

Time: Day 1 up to Month 12

Description: Holter monitoring recorded heart rhythm. Holter monitoring abnormality criteria: any abnormality, atrial fibrillation/flutter, atrial tachycardia, non-sustained ventricular tachycardia (VT), sustained VT and sinus pause.

Measure: Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings

Time: Day 1 up to Month 12

Measure: Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events

Time: Baseline up to Month 12

Description: NIS assessed cranial nerves(nerve 3,6; facial, palate and tongue weakness),muscle weakness (respiratory; neck, elbow(E), wrist(W), finger(F), hip, knee(K) flexion; shoulder, thumb abduction; brachioradialis; E, W, hip, K extension; F spread; toe, dorsal and plantar ankle flexors; toe extensors); score: 0-4, higher score=more weakness, reflexes(biceps and triceps brachii; brachioradialis; quadriceps femoris; triceps surae), index F and great toe sensation(touch pressure, pin-prick, vibration, joint position)score:0=normal,1=decreased or 2=absent. Total score=0-244, higher score=more impairment.

Measure: Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0 to 4 scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment.

Measure: Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than [<] 2) in Neuropathy Impairment Score- Lower Limb (NIS-LL) score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

Measure: Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12

Time: Month 6, Month 12

Description: TQOL= sum of all Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) items,a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on QOL of participants with DN; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). Total TQOL score=-2 to 138;higher score=worse quality of life.

Measure: Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7: scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale:0=no problem, 4=severe problem(except item 32: -2=much better, 0=about same, 2=much worse).Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptom(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12);higher score=greater impairment, for each. Total score=-2 to 138 (higher score=worse QOL).

Measure: Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: NCS: quantitative measures of peripheral nerve dysfunction consists of 5 attributes: peroneal nerve (PN) motor distal latency, PN compound muscle action potential, PN motor conduction velocity, tibial nerve distal motor latency, sural nerve sensory nerve action potential. Normal deviates (Z-score) summated into composite score (higher score=worsened nerve fiber function). Z-score is the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.

Measure: Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: HRDB test was used to evaluate the cardio-vagal response. Participant took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. The main factor affecting HRDB is age, with older patients showing less heart rate variability. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as the normal deviates (Z-score), the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.

Measure: Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12

Time: Baseline, Month 6, Month 12

Description: BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2). mBMI was calculated by multiplying BMI by serum albumin levels [gram/liter (g/L)]. mBMI was measured as kg/m^2*g/L. A progressive decline in mBMI indicated worsening of disease severity.

Measure: Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health and two total scores (physical component summary [PCS] and mental component summary [MCS]. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Measure: Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Echocardiography was used to measure interventricular septal thickness (IVST), posterior left ventricular wall thickness (PLVWT), right ventricular wall thickness (RVWT), left atrial diameter (LAD): anterior-posterior (ant-post), medio-lateral, superior-inferior (sup-inf) and left ventricular end diastolic diameter (LVED), relative LV wall thickness (RLVWT).

Measure: Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Left atrial volume was measured by echocardiography.

Measure: Change From Baseline in Left Atrial Volume at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Cardiac MRI was done to measure left ventricular (LV) end systolic volume, left ventricle (LV) stroke volume.

Measure: Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Fractional shortening (FS) is the fraction of any diastolic dimension that is lost in systole. Percent of FS was calculated as difference between end-diastolic dimension (EDD) and end-systolic dimension (EDS) divided by EDD.

Measure: Change From Baseline in Fractional Shortening at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Cardiac MRI was done to measure left ventricular ejection fraction (LVEF) which was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction.

Measure: Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.

Measure: Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. IVRT is the time between the closure of the aortic valve and the opening of the mitral valve. Mitral deceleration time (MDT) was the time taken from the maximum E point wave to baseline. E wave arises due to early diastolic filling.

Measure: Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: The diameter at the base of the aortic root, the basal ring, is also called the aortic annulus diameter.

Measure: Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Tricuspid peak velocity was measured by echocardiography.

Measure: Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Systolic right ventricular pressure can be estimated on echocardiography by adding right atrial pressure (RAP) to the trans-tricuspid gradient derived from the tricuspid regurgitation velocity.

Measure: Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Doppler principle was used to measure the mitral peak early (E) diastolic transmitral flow, mitral peak atrial (A) contraction velocity and annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity.

Measure: Change From Baseline in Doppler Data at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Ratio of early (E) diastolic transmitral flow velocity and atrial (A) contraction velocity (E/A) and ratio of the early (E) diastolic transmitral flow velocity to the mitral annular velocity (e') (E/e') were estimated.

Measure: Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. QRS score (the sum of QRS voltages in the peripheral leads) was used as an index of "electrical" LV mass.

Measure: Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: LA volume index (LAVI), was the value of LA volume divided by body surface area, to measure LA size.

Measure: Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: NT-proBNP was a cardiac marker which had the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.

Measure: Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12

Time: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12

Description: Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.

Measure: Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Troponin I is a cardiac injury biomarker. Higher concentrations of this marker in blood are associated with heart injury.

Measure: Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12

Time: Baseline, Week 2, Week 6 , Month 3, Month 6, Month 12

3 OPEN-LABEL SAFETY AND EFFICACY EVALUATION OF FX-1006A IN SUBJECTS WITH TRANSTHYRETIN (TTR) AMYLOIDOSIS

This is a Phase 3, open-label study designed to obtain additional long-term safety and efficacy data for oral tafamidis (20 mg soft gelatin capsule) administered once daily (QD). In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. Upon regulatory approval for the treatment of ATTR-PN in their respective country and access to prescription tafamidis, subjects may have been withdrawn from the study. Such subjects were considered study completers.

NCT00925002
Conditions
  1. ATTR-PN
Interventions
  1. Drug: Tafamidis
MeSH:Amyloidosis
HPO:Amyloidosis

In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. --- Val30Met ---

In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. --- Val30Met --- --- Val30Met ---

Primary Outcomes

Measure: Percentage of patients with a change from baseline in Neuropathy Impairment Score (NIS)

Time: Baseline up to 10 years

Measure: Percentage of patients with a change from baseline in Total Quality of Life (TQOL) score

Time: Baseline up to 10 years

Measure: Number or Percentage of patients with a change from baseline in Karnofsky Performance Scale Index

Time: Baseline up to 10 years

Measure: Percentage of patients with a change in subject ambulation as measured by modified Polyneuropathy Disability (mPND) score

Time: Baseline up to 10 years

Secondary Outcomes

Measure: Incidence of treatment emergent adverse events from baseline through 10 years

Time: Baseline up to 10 years

Measure: Number or percentage of patients with change from baseline in Clinical Laboratory parameters

Time: Baseline up to 10 years

Measure: Number of patients with change in ECG parameters

Time: Baseline up to 10 years

Measure: Number or percentage of patients with change from baseline in Vital sign measurements

Time: Baseline up to 10 years

Measure: Descriptive summary of physical examination findings for patients through 10 years

Time: Baseline up to 10 years

Measure: Descriptive summary of concomitant medication use for patients through 10 years

Time: Baseline up to 10 years

4 The Effect On Transthyretin Stabilization, Safety, Tolerablity, Efficacy And Pharmacokinetics Of Orally Administered Tafamidis In Transthyretin Amyloid Polyneuropathy Patients With V30m Or Non-v30m Transthyretin: A Phase Iii, Open-label Study

Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer.

NCT01435655
Conditions
  1. Transthyretin Familial Amyloid Polyneuropathy
Interventions
  1. Drug: tafamidis
MeSH:Polyneuropathies Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis
HPO:Amyloidosis Lattice corneal dystrophy Motor polyneuropathy Polyneuropathy

The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer. --- V30M ---

The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer. --- V30M --- --- V30M ---

Inclusion Criteria: - Transthyretin amyloid polyneuropathy with V30M or non-V30M transthyretin mutation. --- V30M ---

Inclusion Criteria: - Transthyretin amyloid polyneuropathy with V30M or non-V30M transthyretin mutation. --- V30M --- --- V30M ---

Primary Outcomes

Description: TTR tetramer level for each plasma sample was assessed using a validated immunoturbidimetric assay before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer average concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.

Measure: Number of Participants With Transthyretin (TTR) Stabilization at Week 8 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay

Time: 8 weeks

Secondary Outcomes

Description: The NIS provides a total body single score of neuropathic deficits (score range: 0-122, higher score = more deficit), comprising subset scores for cranial nerves, muscle weakness, reflexes, and sensation (based on mean of 2 scores in 1 week period; each item scored separately for left and right). The NIS-LL is a subscale that provides a score for the lower limbs functions (muscle weakness, reflexes and sensation in great toe) and has a score range of 0-44 (higher score = more deficit). The NIS-UL is a subscale that provides a score for the upper body functions (muscle weakness [including cranial nerves], reflexes and sensation in finger) and has a score range of 0-78 (higher score = more deficit). The components for cranial nerves and muscle weakness are scored from 0 (Normal) to 4 (Paralysis), and those for reflexes and sensation from 0 (Normal) to 2 (Absent). For all items, higher scores indicate greater impairment.

Measure: Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: Norfolk QOL-DN is a 35-item participant-rated questionnaire. It consists of 5 domains: Physical Functioning/Large Fiber [score range: -4 - 56] , Activities of Daily Living (ADL) [0 - 20], Symptoms [0 - 32], Small Fiber [0 - 16] and Autonomic [0 - 12]. Total of quality of life (TQOL) score is the sum of all five domains with a range of -4 to 136 (Pfizer Data Standards). Higher scores on each item of the Norfolk QOL-DN TQOL indicate worse quality of life.

Measure: Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.

Time: Baseline, Week 26, Week 52, Week 78

Description: The Σ7 NTs nds measures primarily large-fiber function. It is a composite score derived from five NCS attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with VDT obtained in great toes by Quantitative Sensory Testing (QST), and HRDB value. It is defined as 7 times the mean of non-missing values of, the five normal deviates of NCS, HRDB, and average normal deviate for VDT of toes. Score was determined through reference to normal values for age, sex, height and abnormalities scored. Total score range is approximately -26 to 26, where higher score=worse nerve function.

Measure: Change From Baseline in Summated 7 Nerve Tests Normal Deviate Score (∑ 7 NTs Nds) as Measured by Nerve Conduction Studies (NCS), Vibration Detection Threshold (VDT) and Heart Rate Response to Deep Breathing (HRDB) at Week 26, Week 52, and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: The Σ3 NTSF nds measures small-fiber function. It is a composite score defined as 3 times the mean of non-missing values of normal deviates of cooling threshold for lower limbs, heat pain intermediate response for lower limbs, and HRDB. The total score range is approximately -11.2 to 11.2, with a higher score demonstrating worse nerve function.

Measure: Change From Baseline in Summated 3 Nerve Tests Small Fiber Normal Deviate Score (∑ 3 NTSF Nds) as Measured by Cooling and Heat Pain Thresholds by QST and HRDB at Week 26, Week 52 and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: The mBMI was calculated by multiplying the BMI (the weight in kilograms divided by the square of the height in meters) by serum albumin level (gram/liter). Change in mBMI was calculated as the mBMI at the given week minus the Baseline mBMI.

Measure: Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study

Time: Baseline, Week 8, Week 26, Week 52, End of Study

Description: Ambulatory status was evaluated using walking ability scale in polyneuropathy disability score. The ambulatory status was evaluated as: 0=Good, 1=Sensory disturbances in the feet but able to walk without difficulty, 2=Some difficulties with walking but can walk without aid, 3a=Able to walk with 1 stick or crutch, 3b=Able to walk with 2 sticks or crutches, 4=Not ambulatory, confined to a wheelchair or bedridden.

Measure: Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The TTR tetramer level for each plasma sample was measured before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.

Measure: Number of Participants With Transthyretin (TTR) Stabilization at Week 26, Week 52, and Week 78 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay

Time: Baseline, Week 26, Week 52, Week 78

Other Outcomes

Description: Mean plasma concentration of tafamidis at 3 hours after administration

Measure: Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78

Time: Week 8, Week 26, Week 52, Week 78

5 Cross-sectional, Non-interventional Burden Of Disease (Bod) Study In Patients With Transthyretin Familial Amyloidosis Polyneuropathy (Ttr-fap) Or Transthyretin Cardiomyopathy (ttr-cm) And Caregivers

This study is an online (web-based) or paper-based survey for patients with transthyretin familial amyloidosis polyneuropathy (TTR-FAP) and caregivers. The results will be used to describe the emotional, physical, and financial impact of having TTR-FAP or caring for someone who has the disease.

NCT01604122
Conditions
  1. Transthyretin Familial Amyloidosis Polyneuropathy (TTR-FAP)
  2. Transthyretin Cardiomyopathy (TTR-CM)
  3. Familial Amyloid Cardiomyopathy
  4. Senile Systemic Amyloidosis (SSA)
Interventions
  1. Other: No drug
  2. Other: No drug
MeSH:Polyneuropathies Amyloid Neuropathies Cardiomyopathies Amyloidosis, Familial Amyloidosis
HPO:Amyloidosis Cardiomyopathy Motor polyneuropathy Polyneuropathy

In this outcome, number of participants with each type of resulted mutation type (Val30Met, wild type TTR, Phe64Leu, Ser77Tyr, Thr60Ala or other than these) were reported. --- Val30Met ---

Primary Outcomes

Description: Main characteristics included were education level and employment status which were asked from all participants and caregivers. Type of job (full-time, part-time) was asked only from those participants and caregivers who provided their employment status as employed. Those who were unemployed reported their cause of unemployment, whether it was due to ATTR or not.

Measure: Demographical Characteristics of Participants

Time: Baseline (Day 1)

Description: Duration of disease was defined as the time from diagnosis of disease until baseline visit. This outcome measure was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Disease Duration

Time: Baseline (Day 1)

Description: Genetic mutation leads to misfolding of protein transthyretin (TTR) which results in ATTR. In this outcome, number of participants with each type of resulted mutation type (Val30Met, wild type TTR, Phe64Leu, Ser77Tyr, Thr60Ala or other than these) were reported. This outcome was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Mutation Type

Time: Baseline (Day 1)

Description: TTR protein is primarily synthesized in the liver. Liver transplantation was considered as one of the measure to eliminate the main source of variant TTR. In the study, participants who were diagnosed with ATTR were asked for their liver transplantation status (whether they had transplantation or not). In this outcome measure, number of participants with liver transplant status were reported. This outcome was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Liver Transplantation Status

Time: Baseline (Day 1)

Description: Family history of participants diagnosed with ATTR was assessed to determine whether family history of ATTR was a significant risk factor for ATTR or not. This outcome was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Number of Participants With Family History of ATTR

Time: Baseline (Day 1)

Description: Mobility, i.e., ability to walk was assessed as a part of loss of functioning in the participants diagnosed with ATTR. In this outcome, number of participants with their different mobility status along with the use of mobility aids (able to walk normally, some problems with feet but able to walk without difficulty, some difficulty walking but can walk without help, confined to bed all the time, need 1 cane or crutch to walk, need 2 canes/crutches or a walker to walk) were reported.

Measure: Disease Characteristics of Participants: Mobility Status

Time: Baseline (Day 1)

Description: SF-12 was a patient reported outcome survey that represented overall health status by measuring 8 health-related aspects of an individual: Body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Responses on the SF-12 were also used to calculate 2 summary scores: Physical component score (PCS) and mental component score (MCS). The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), where 100 indicated good health condition.

Measure: 12-Item Short-Form Health Survey (SF-12) Scores

Time: Baseline (Day 1)

Description: HADS: participant rated 14-item questionnaire with 2 subscales; HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D). HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for each subscale; higher score indicating greater severity of anxiety and depression symptoms.

Measure: Hospital Anxiety and Depression Scale (HADS): Depression and Anxiety Subscale Scores

Time: Baseline (Day 1)

Description: EQ-5D-3L: participant rated questionnaire to assess generic health status in two parts: single utility score and visual analog scale. For utility score, participants rated their current health state on 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression with each dimension having three levels of function: 1 indicates no problem; 2 indicates some problem; 3 indicates extreme problem. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score was transformed and results in a total score range of 0.05 to 1.00; higher scores indicating a better health state.

Measure: Euro Quality of Life (EQ-5D-3L)- Health State Profile Utility Score

Time: Baseline (Day 1)

Description: EQ-5D: participant rated questionnaire to assess generic health status in two parts: single utility score and visual analog scale. The VAS component rated the current health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicating a better health state.

Measure: Euro Quality of Life (EQ-5D-3L)- Visual Analog Scale (VAS) Score

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asked about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Percentage of work time missed of participants were recorded and reported.

Measure: Work Productivity and Activity Impairment- Specific Health Version (WPAI-SH): Percent of Work Time Missed

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asks about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Component scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. The computed percentage range for each sub-scale was from 0-100, where higher numbers indicating greater impairment and less productivity.

Measure: Work Productivity and Activity Impairment- Specific Health Version: Percent Impairment While Working

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asked about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Component scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. The computed percentage range for each sub-scale was from 0-100, where higher numbers indicating greater impairment and less productivity.

Measure: Work Productivity and Activity Impairment- Specific Health Version: Percent Overall Work Impairment

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asks about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Component scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. The computed percentage range for each sub-scale was from 0-100, where higher numbers indicating greater impairment and less productivity.

Measure: Work Productivity and Activity Impairment- Specific Health Version: Percent Activity Impairment

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR and caregivers was assessed by questions concerning a variety of different types of treatment and resources including outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (for example, costs of travel to receive care).

Measure: Healthcare Resource Use Survey: Number of Outpatient Visits to Healthcare Providers

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR and caregivers was assessed by questions concerning a variety of different types of treatment and resources including outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (for example, costs of travel to receive care).

Measure: Healthcare Resource Use Survey: Number of Hospitalizations

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR and caregivers was assessed by questions concerning a variety of different types of treatment and resources including outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (for example, costs of travel to receive care).

Measure: Healthcare Resource Use Survey: Number of Emergency Care Visits

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR was assessed by questions concerning a variety of treatments and resources included outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs. Number of participants (diagnosed with ATTR) who visited non-medical practitioners (nutrition consultant/dietician, chiropractor, acupuncturist, massage therapist, occupational therapist or other than these) for symptomatic treatments were reported.

Measure: Healthcare and Resource Use Survey: Symptomatic Treatment of Participants

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR was assessed by questions concerning a variety of treatments and resources included outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs. Number of visits of participants (diagnosed with ATTR) who visited non-medical practitioners (nutrition consultant/dietician, chiropractor, acupuncturist, massage therapist, occupational therapist or other than these) for symptomatic treatments were reported.

Measure: Healthcare Resource Use Survey: Number of Symptomatic Treatment Visits

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR was assessed by questions concerning a variety of treatments and resources included outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (expenditure on nutritional supplements, non-prescription medications and travel to receive medical care).

Measure: Healthcare Resource Use Survey: Out-of-Pocket Costs

Time: Baseline (Day 1)

Description: Participants diagnosed with ATTR rated their pain due to the health condition based on 3 items: pain right now, average pain in the past week, and worst pain in the past week prior to baseline visit. All 3 items were rated on an 11-point numeric rating scale ranging from 0=none to 10=severe pain, where higher scores indicated severe pain.

Measure: Participants Pain Score

Time: Baseline (Day 1)

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of neuropathy on the quality of life of participants diagnosed with ATTR. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: activities of daily living, large fiber neuropathy/physical functioning, small fiber neuropathy, autonomic neuropathy, and symptoms. TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life. This outcome measure was planned to be analyzed only for the reporting arm of participants diagnosed with ATTR.

Measure: Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Total Quality of Life (TQOL): Total Scores

Time: Baseline (Day 1)

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of neuropathy on the quality of life of participants diagnosed with ATTR. It was summarized in 5 domains: (1) Activities of daily living (score ranges from 0 to 20, where higher score=worse quality of life); (2) Large fiber neuropathy/physical functioning (score ranges from -2 to 58, where higher score=worse condition); (3) Small fiber neuropathy (score ranges from 0 to 16, where higher score=worse condition); (4) Autonomic neuropathy (score ranges from 0 to 12, where higher score=worse condition) and (5) Symptoms (score ranges from 0 to 32, where higher score=less symptoms of disease). Total possible score range= -2 to 138, where higher score=worse quality of life. This outcome measure was analyzed only for the participants diagnosed with ATTR.

Measure: Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life: Subscale Scores

Time: Baseline (Day 1)

Description: KCCQ was a 23-item participant-completed questionnaire that assessed health status and health-related quality of life (HRQoL) in participants with heart failure. It was quantified in to following 10 summary scores: physical limitation, symptom frequency, symptom severity, and symptom stability, total symptoms, quality of life, social interference, self-efficacy, overall summary and clinical summary. Each summary score was scaled to range from 0 (minimum) to 100 (maximum), with higher scores representing greater disability. Total score ranged from 0 to 100, where higher scores indicated better functioning, fewer symptoms, and better disease specific quality of life.

Measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores

Time: Baseline (Day 1)

Description: ZBI was a 22-item questionnaire designed to evaluate five broad aspects of caregiver burden in terms of personal and role strain associated with caregiving. Five broad aspects were: burden in the relationship, emotional well-being, social and family life, finances, loss of control over one's life. Each item rated on a 5 point scale anchored at 0 for "never" and 4 for "nearly always." Total score ranges from 0-88 with higher scores indicating increased burden of care.

Measure: Zarit Burden Interview (ZBI): Total Scores

Time: Baseline (Day 1)

Description: A questionnaire designed to evaluate aspects of caregiver burden in terms of personal and role strain associated with caregiving. Total score of ZBI scale ranges from 0-88 with higher scores indicating increased burden of care. Five subscale scores were also calculated: (1) Burden in the relationship (consist of 6-items, ranging from 0 to 24 where higher scores indicating increased burden in relationship); (2) Emotional well-being (consisting of 7-items, ranging from 0 to 28 where higher scores indicating worse condition; (3) Social and family life (consisting of 4-items, ranging from 0 to 16 where higher scores indicating worse life condition); (4) Finances (consisting of a single item, scored from 0 to 4 where higher scores indicating worse financial condition); and (5) Loss of control over one's life (consisting of 4-items, ranging from 0 to 16 where higher scores indicating worse control over life).

Measure: Zarit Burden Interview: Subscale Scores

Time: Baseline (Day 1)

Description: Caregivers completed a series of questions related to the number of hours per week spent on providing care and support to the participants diagnosed with ATTR.

Measure: Caregiver Burden Items Assessment: Number of Hours Per Week Spent in Care of the Participants With ATTR

Time: Baseline (Day 1)

Description: Caregivers completed a series of questions related to the loss in their working time while providing care and support to the participants diagnosed with ATTR.

Measure: Caregiver Burden Items Assessment: Work Time Lost

Time: Baseline (Day 1)

Description: Caregivers completed a series of questions related to the total cost spent on providing healthcare support to participants diagnosed with ATTR.

Measure: Caregiver Burden Items Assessment: Total Cost

Time: Baseline (Day 1)

6 Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP): An International, Multicenter, Epidemiological Protocol

An International, multicenter, epidemiological observational study investigating the prevalence of Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP) in participants with small fiber polyneuropathy of no obvious etiology.

NCT01705626
Conditions
  1. Polyneuropathy, Amyloid
  2. Neuropathic Pain
  3. Cardiac Failure
  4. Orthostatic Hypotension
  5. Gastrointestinal Disorders
MeSH:Digestive System Diseases Gastrointestinal Diseases Neuralgia Polyneuropathies Hypotension, Orthostatic Amyloid Neuropathies Hypotension Heart Failure
HPO:Abnormal left ventricular function Abnormality of the gastrointestinal tract Congestive heart failure Hypotension Motor polyneuropathy Orthostatic hypotension Polyneuropathy Right ventricular failure

It accounts several thousand cases worldwide, with Val30Met mutation identified in most patients and with endemic foci in Portugal, Sweden and Japan. --- Val30Met ---

Primary Outcomes

Description: Dry Blood Spot (DBS) samples will be genetically validated via combination of Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification (MLPA) of TTR gene

Measure: Epidemiological analysis of prevalence of the TTR FAP in participants with small fiber polyneuropathy of no obvious etiology.

Time: 3 years

Secondary Outcomes

Description: Samples carrying a mutation in the TTR gene will be biochemically analyzed via liquid chromatography multiple reaction monitoring MS and compared with a merged control cohort, in order to establish TTR mutation-specific biomarker/s.

Measure: Establishment of a biomarker in TTR-positive cohort

Time: 3 years

7 Biomarker for Transthyretin-Related Familial Amyloidotic Polyneuropathy - An International, Multicenter, Epidemiological Protocol

International, multicenter, observational, longitudinal study to identify biomarker/s for the development of a new MS-based biomarker for the early and sensitive diagnosis of Transthyretin-Related Familial Amyloidotic Polyneuropathy from blood and number of correctly identified patients with Transthyretin-Related Familial Amyloidotic Polyneuropathy

NCT02713880
Conditions
  1. Transthyretin Amyloidosis
  2. Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
  3. Transthyretin Amyloid Cardiopathy
MeSH:Polyneuropathies Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis
HPO:Amyloidosis Lattice corneal dystrophy Motor polyneuropathy Polyneuropathy

Even though more than 100 point mutations are known to cause the disease, the most common amino acid change is V30M. --- V30M ---

Primary Outcomes

Measure: Development of a new MS-based biomarker for the early and sensitive diagnosis of Transthyretin-Related Familial Amyloidotic Polyneuropathy from blood

Time: 36 months

Secondary Outcomes

Measure: Number of correctly identified patients with Transthyretin-Related Familial Amyloidotic Polyneuropathy

Time: 36 months

8 Project to Accelerate the Diagnosis of TTR Amyloidosis by Use of Molecular Biology in First Intention

Peripheral neuropathies are diseases that affect the nervous system outside the brain and spinal cord, their prevalence is 1% in the general population, the causes are extremely varied with more than 200 identified causes; the main ones are diabetes, excessive alcohol consumption and chemotherapy. They may be sometimes disabling but generally preserve autonomy. Transthyretin amyloidosis is a rare multisystematic hereditary disease with autosomal dominant transmission. They present usually as a peripheral neuropathies (FAP). They are due to a point mutation of the transthyretin gene (chr 18q). FAP is secondary to endoneurial amyloid deposits and are characterized by a slowly progressive sensory, motor and autonomic. FAP is the most severe hereditary polyneuropathy of the adult are irreversible and fatal within 5 to 12 years from onset. Most frequent mutation of TTR gene is located on the second exon; but more than 100 mutations have been reported. Prevalence of FAP is 1 per 1 million inhabitants. They have been reported until 1990s' in four endemic areas North of Portugal, Sweden, Japan and Majorca. In these areas, diagnosis is facilitated because of the stereotypical presentation : a length-dependent polyneuropathy with predominant involvement of thermal and pain sensations and autonomic dysfunction, early onset in the third decade and a predominant Met30 TTR mutation. Positive family history is frequent 85% (one of the parents is affected). Diagnosis requires detection of TTR mutation by molecular biology (blood sample) and characterization of amyloid deposit on labial salivary gland biopsy.

NCT03373370
Conditions
  1. Polyneuropathy
  2. Diagnosis
  3. Idiopathic Progressive Neuropathy
MeSH:Polyneuropathies Amyloidosis
HPO:Amyloidosis Motor polyneuropathy Polyneuropathy

Conversely to endemic areas, look for V30M mutation is not enough to exclude TTR-FAP, TTR gene sequencing is required. --- V30M ---

Primary Outcomes

Description: Rate of amyloidogenic TTR mutation in progressive idiopathic polyneuropathy

Measure: Rate of amyloidogenic TTR mutation

Time: 1 day

Secondary Outcomes

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : disabling neuropathy (including ataxic).

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy

Time: 1 day

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Time: 1 day

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

Time: 1 day

9 An Adaptive, Open-Label Study to Evaluate the Biodistribution of 89Zirconium-labelled GSK2398852 in the Heart and Other Organs of Patients With Transthyretin Cardiomyopathy (ATTR-CM) Using Positron Emission Tomography (PET) Imaging

The principal aim of this study is to investigate the cardiac uptake of 89Zr-GSK2398852 in subjects with transthyretin cardiomyopathy amyloidosis (ATTR-CM), and its biodistribution to other organs. Low doses of GSK2398852 will be co-administered at levels not high enough for therapeutic benefit. This study will be conducted in two parts: Part A and Part B. Subjects in Part A will participate in up to two dosing sessions and subjects in Part B will participate in one dosing session. Subjects will undergo up to 3 PET scans at varying intervals after 89Zr-GSK2398852 administration. The total duration of study will be approximately 3 to 4 months for subjects in Part A and approximately 2 months for subjects in Part B. Part B of the study will be triggered based on data obtained in Part A and other emerging data.

NCT03417830
Conditions
  1. Amyloidosis
Interventions
  1. Drug: GSK2315698 (CPHPC)
  2. Drug: GSK2398852 (unlabeled anti-SAP mAb)
  3. Drug: 89Zr-GSK2398852 (89Zr-labeled anti-SAP mAb)
MeSH:Amyloidosis
HPO:Amyloidosis

b) Hereditary ATTR amyloidosis (example, TTR Val30Met) should have a known amyloidogenic TTR mutation demonstrated by genotyping and is recognized to be primarily associated with cardiomyopathy and one of the following: i) Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarized light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis. --- Val30Met ---

Primary Outcomes

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852.

Measure: Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented.

Measure: Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4 and 5

Description: SUV in focal anatomical regions of the heart was planned to be measured.

Measure: Part B: Peak SUV in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV in focal anatomical regions of the heart was planned to be measured.

Measure: Part B: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.

Measure: Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.

Measure: Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4 and 5

Description: SUV of whole heart was planned to be measured.

Measure: Part B: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV of whole heart was planned to be measured.

Measure: Part B: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Secondary Outcomes

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as abdominal skin and skin of the back. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre hotspot. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot

Time: Session 1: Days 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as thyroid gland-goitre hotspot, abdominal skin and skin of the back. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4 and 5

Description: SUV of focal radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV of focal radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, and thigh. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre

Time: Session 1: Days 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for testes. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes

Time: Session 1: Days 4, 5 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, thigh, and thyroid gland- goitre. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4, and 5

Description: SUV of total radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV of total radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Total Radioactivity Uptake After an Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Description: Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). PK Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed.

Measure: Part A: Maximum Concentration in Plasma (Cmax) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: Cmax of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Time Associated With Cmax (Tmax) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: Tmax of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Clearance of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: Clearance of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Terminal Half-life (T1/2) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: T1/2 of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: AUC(0 to t) of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: AUC(0 to Infinity) of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK)

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: Cmax of 89Zr-GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: Tmax of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: Tmax of 89Zr-GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: T1/2 of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: T1/2 of 89Zr- GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852.

Measure: Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time: Up to Day 26 of the last session

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention.

Measure: Part B: Number of Participants With AEs and SAEs

Time: Up to Day 26

Description: Rash was graded as Grade 1 to Grade 4 based on symptoms and body surface area (BSA) affected; Grade 1: <10 percent (%) BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: >30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement).

Measure: Part A: Number of Participants With Skin Rashes

Time: Up to Day 26 of the last session

Description: Rash was planned to be graded as Grade 1 to Grade 4 based on symptoms and BSA affected; Grade 1: <10% BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: >30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement).

Measure: Part B: Number of Participants With Skin Rashes

Time: Up to Day 26

Description: The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class are presented.

Measure: Part A: Number of Participants With Cardiac Adverse Events

Time: Up to Day 26 of the last session

Description: The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class were planned to be reported.

Measure: Part B: Number of Participants With Cardiac Adverse Events

Time: Up to Day 26

Description: Number of participants with any infusion related reactions are presented.

Measure: Part A: Number of Participants With Infusion Related Reactions

Time: Up to Day 26 of the last session

Description: Number of participants with any infusion related reactions were planned to be reported.

Measure: Part B: Number of Participants With Infusion Related Reactions

Time: Up to Day 26

Description: Blood samples were collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)

Time: Session 1: Baseline (Day 1 Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26; Session 2: Day 1- Pre-dose, Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26

Description: Blood samples were planned to be collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part B: Change From Baseline in Cardiac Troponin T and NT-ProBNP

Time: Baseline and up to Day 26

Description: 12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Measure: Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings

Time: Up to Day 26 of the last session

Description: 12-lead ECGs were planned to be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal 12-lead ECG Findings

Time: Up to Day 26

Description: Continuous inpatient cardiac monitoring was performed via remote cardiac telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Measure: Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry

Time: Up to Day 26 of the last session

Description: Continuous inpatient cardiac monitoring was planned to be performed via remote cardiac telemetry device.

Measure: Part B: Number of Participants With Abnormal Inpatient Cardiac Telemetry

Time: Up to Day 26

Description: Continuous outpatient cardiac monitoring was performed via remote cardiac bodyguardian telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Measure: Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry

Time: Up to Day 26 of the last session

Description: Continuous outpatient cardiac monitoring was planned to be performed via remote cardiac bodyguardian telemetry device.

Measure: Part B: Number of Participants With Abnormal Outpatient Cardiac Telemetry

Time: Up to Day 26

Description: SBP and DBP were measured in a semi-supine position after 5 minutes of rest for the participant. Potential Clinical Importance (PCI) ranges for the SBP and DBP were as follows: SBP- <90 and >180 millimeters of mercury (mmHg), and DBP- <30 and >110 mmHg.

Measure: Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time: Up to Day 26 of the last session

Description: SBP and DBP were planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal SBP and DBP

Time: Up to Day 26

Description: Temperature was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for temperature was as follows: temperature- >37.5 degree celsius.

Measure: Part A: Number of Participants With Abnormal Temperature

Time: Up to Day 26 of the last session

Description: Temperature was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal Temperature

Time: Up to Day 26

Description: Respiratory rate was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for the respiratory rate was as follows: respiratory rate- <12 and >25 breaths per minute.

Measure: Part A: Number of Participants With Abnormal Respiratory Rate

Time: Up to Day 26 of the last session

Description: Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal Respiratory Rate

Time: Up to Day 26

Description: Pulse rate were measured in a semi-supine position after 5 minutes of rest for the participant. PCI range for the pulse rate was as follows: pulse rate- <35 and >140 beats per minute (bpm).

Measure: Part A: Number of Participants With Abnormal Pulse Rate

Time: Up to Day 26 of the last session

Description: Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal Pulse Rate

Time: Up to Day 26

Description: A full and brief physical examination was performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).

Measure: Part A: Number of Participants With New Abnormal Physical Examination Findings

Time: Session 1: At screening (within 35 days of Anti-SAP treatment of session 1), Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11; Session 2: Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11

Description: A full and brief physical examination was planned to be performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).

Measure: Part B: Number of Participants With New Abnormal Physical Examination Findings

Time: At screening (within 35 days of Anti-SAP treatment), Days 1, 3, 5, 8 and 11

Description: Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameters.

Measure: Part B: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Hematocrit

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Hematocrit

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Hemoglobin

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Hemoglobin

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameters: Erythrocytes and Reticulocytes. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameters.

Measure: Part B: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Potassium, Sodium and Urea. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: Albumin, Protein

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: ALP, ALT and AST. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: ALP, ALT, AST

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: Direct Bilirubin, Bilirubin, Creatinine. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Urine samples were collected to analyze urinalysis parameters including glucose, protein, blood and ketones.

Measure: Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones

Time: Up to Day 26 of the last session

Description: Urine samples were collected to analyze urinalysis parameters including specific gravity and potential of hydrogen.

Measure: Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen

Time: Up to Day 26 of the last session

Description: Urine samples were planned to be collected to analyze the urinalysis parameters.

Measure: Part B: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones

Time: Up to Day 26

Description: Urine samples were planned to be collected to analyze the urinalysis parameters.

Measure: Part B: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen

Time: Up to Day 26


HPO Nodes


HP:0011024: Abnormality of the gastrointestinal tract
Genes 2267
RPS19 PRKRA ND4 SLC1A4 GRHL3 RSPH4A EDNRB LPIN2 MCM6 COG4 PGM3 FANCB LIPA FOXG1 PRNP LBR EEF1A2 IRF1 RHBDF2 NTRK1 GP1BB MAPT EXTL3 GDNF NDUFS1 SEC24C DKK1 PAH CDH11 SYNJ1 CHN1 CTRC ATXN2 PEX11B OFD1 BLK FGF20 WWOX NSD2 FBXL4 TRIP13 FTSJ1 SOX10 ADH1C FOXH1 MCC MAGEL2 GDAP2 MET NEB RAD51 TP53 GFI1B ERCC4 POLG FGB SMARCD1 HNRNPH2 ASXL1 LBR BRCA1 PSTPIP1 SEC31A MLH3 NECAP1 NUP62 SIN3A NSD1 ERCC2 TSC2 PLA2G6 SPINK5 FANCL DDOST STX3 EMC1 XYLT2 NEK1 FLNB VCP BRAF FBLN5 PAX7 MAP2K1 MAN2B1 ARSA TIMM8A PAX3 SEMA3E RASGRP1 TPM2 NEUROD2 TMEM67 FGFR2 LRRC56 SPOP DPYS DNAJC21 TRIP4 PTDSS1 MYF6 ACTG2 PEX19 PANK2 TERF2IP TNFRSF13C GLI3 RPL26 SBDS MGMT RERE KLLN ARNT2 FANCM SLC13A5 AXIN2 TNFAIP3 KIF7 FOXP3 MEFV MYCN TGFBR2 CIITA SLC2A10 UBR1 OSGEP EDNRB IARS1 ENG PDGFRL GLI2 DNAJB13 CACNA1A STAT6 FLT1 RNASEH1 TRAPPC12 NOTCH3 GAS1 ATXN8OS ANKRD11 SPG7 SURF1 HLA-DRB1 SIX6 JAG1 ARL13B EDNRB PALB2 VANGL1 SLC9A6 GBE1 SALL4 PNKD DGUOK FANCG RAD51C ATN1 TGIF1 MYO1H ELANE ND5 RPS19 H19-ICR PIGO SHH F8 ARHGAP31 IDH2 SPG21 CDON CDH1 NEDD4L SIX3 CYP27A1 MITF MST1 RAI1 LAMA2 PHGDH TRNV PDGFRB QDPR DNAAF4 FAT4 ORC4 ZIC2 HFE SDHD BMPR1A GABRG2 SQSTM1 ISL1 TNFRSF13B FGF8 SELENON POLR1D MYOT SFTPA1 SHH SKIV2L COL18A1 STXBP1 SON SLC25A22 GALC HMBS RET RRM2B ABCD4 MMEL1 IGF2R NODAL LRP12 SKI NOS1 BUB1B ERAP1 SMC1A AXIN2 ADD3 GAS1 STAC3 TRIP4 CIITA SLC25A13 PRTN3 PIGN NTRK2 TRNF PKHD1 TDGF1 TIMM22 DYRK1A FLCN UBE3B CHRNG LAMC2 DNM2 TSR2 IL12A ALDH18A1 POLG CDKN1A HCN1 DCTN4 IRF5 CCN2 ARL3 WNT7A DKC1 GMNN BAP1 APC ACD CHCHD10 ROR2 SIX3 CYP7B1 FANCB ZEB2 RPL10 KLF6 FRMPD4 NUP107 SMAD3 F2 CENPT APC REEP1 NRTN COL13A1 IRF9 ACSL4 BUB3 GAS8 WDR35 LIG4 MLH1 CCDC40 GNA11 DYNC2H1 PLEC NF2 SACS TGFB3 SDHD WT1 MRPS34 STAT1 POLR3B PHOX2B TMEM237 FBN1 NRXN1 PTPRJ GLUD2 HPRT1 ABL1 GP9 CDKL5 LMNA SLC35A2 PQBP1 TRNL1 PTS EDNRB ABCC6 PDGFRA VARS1 SETD5 SYNGAP1 PPP3CA NCF4 LRBA DRC1 FERMT1 SNCA COX7B PEX12 GDF2 DNAH5 CASP8 TBK1 PLG MAN2B1 FXN SNCA TP53 LAMC2 BMP4 GP9 KATNIP FANCD2 GBA PYGL HCCS IRF5 APPL1 UPF3B PIGV TRNQ RRM2B APC RFC2 NCF1 HPS1 IRF6 TDGF1 SEMA3C WAS PRKCG TANGO2 USP7 CDKN2A SEMA3E LRRC8A SHANK3 SLC35A2 DDX59 CCNO ZNF711 PHOX2B SOX2 RAD21 CDK8 APC CC2D2A JAK2 CLCN1 CENPF BUB1 RAD51 DKC1 CYBB RAD54B AFF4 FIG4 EPCAM SMG9 SLC6A8 REEP1 SRC CTNND1 ALDH18A1 TTC7A FOXH1 BMP2 EOGT DYSF FREM1 ND1 ITGA8 GPHN GLMN SRP54 MYD88 EIF4G1 ARF1 NPM1 PTEN PHOX2B TP53 SMAD4 MTTP SOX3 REV3L MLH1 WAC AIRE ITGA6 STRA6 NDUFB8 FGFR2 FANCC WFS1 DHCR7 ADAMTS2 PTCH1 MEN1 POLE MMP1 COLQ RPL27 CC2D2A F7 MGME1 ADAM17 CRYAB MID1 CLCN4 MED17 GPC3 PALLD ATXN10 GAS1 WASHC5 MDM2 INTU GALC POLR3B RERE ERLIN2 KBTBD13 TP53 MKS1 TARDBP LIFR SHH MEFV IL10RB ACVRL1 MPL FAT4 PRKRA DNAI2 DNAJB6 AKT1 NFIX NFKB2 DEAF1 DALRD3 XYLT1 PEX12 ITGA2B TAF1 FOXF1 SQSTM1 NALCN TNFRSF13B GRIP1 PIGW TGIF1 SMC3 RPS6KA3 NOP56 EYA1 APC2 CTNS TCTN3 FGFR1 PPOX F10 SLC52A3 PKHD1 MAPT ODC1 TPRKB IL12A KRT18 ASCC1 GLRB TDGF1 GUCY1A1 FARS2 TRNW RPL18 PHOX2B TGIF1 TBP NOTCH3 WDR4 EHMT1 RPGRIP1L TRNK CEP120 CYP7B1 DNMT3B SF3B4 MEOX1 CEP290 LMNB1 PCSK1 WDR26 CFC1 UBTF TANGO2 MSH6 SDHB RARS1 CISD2 TRIM28 AKR1D1 AP1B1 USB1 POLR3A SMC1A RSPH1 AKR1D1 TPM3 COL3A1 ALDOB RMRP DLL1 GNB5 MPZ SDHB NXN CEP57 GP1BB ENG SALL4 SEMA3D MINPP1 CASP10 PTPN22 NTHL1 COL7A1 LMOD1 HLA-DQA1 TERT GLIS3 POGZ F8 FOXH1 TRNL1 NOTCH2 NRXN1 CD81 NODAL DNAH9 DNAJC13 TBC1D23 RAB39B ANTXR2 F13B SCN8A NEB ORC6 C12ORF65 MECR WNT2B TYMP SNCA DSP KCNJ11 MLXIPL HLA-DRB1 CHMP1A SLC37A4 FGFR1 CCND1 CPLX1 SLC5A1 ITGB3 RYR1 ODAD4 FGF8 DMD CYBB STAG1 APC KRAS F9 ZFYVE26 SUFU DISP1 PEX13 GAS1 GPC3 CEL SCN4A TP63 ASCL1 FBLN5 ATP2A2 UFD1 CHEK2 FREM2 AAGAB LMNA CPLANE1 DLL1 POLD1 CARMIL2 EIF2AK3 APC L1CAM CCDC65 GABRB2 FAN1 DAB1 RAD21 FOXG1 G6PC MSH2 CYP7B1 MUC5B EDN3 EWSR1 SPRTN ACTG2 SDHC CDON SLC52A2 ADAR CD79A CFTR MED12 TMEM67 INPP5E CCBE1 USP9X LRP2 MATR3 RPGR TMTC3 FREM1 SPECC1L TTC37 KIF5A RLIM SNAI2 PIK3CD NBN PHOX2B BRAF CACNA1B VAMP1 TCTN1 FANCE PMP22 TJP2 RAD21 GPC4 SCN4A ARL6 SERPINH1 GLI2 NBN HIVEP2 MPI PEX26 DISP1 DNAAF5 BRIP1 POLG NF1 FUS TGFB2 FGF8 PSAP GABRA5 AP1S1 CHST14 WRN BCR POLG SERPINA1 ATAD1 DNAJB6 SRCAP PRPS1 DCX GP1BA TRNS2 NIPBL CEP41 MYO9A ARMC9 ANTXR2 TWIST1 TOP3A ZAP70 TK2 ATXN1 SYP MYRF GNAS ND1 BRCA2 ZEB2 NODAL NEK1 LETM1 CACNA1G USP9X KRAS LAMA3 INAVA APP MAFB BRCA1 ATXN3 PEX3 IL1B FMR1 PANK2 PLAA CD19 UBAC2 RETREG1 COX1 HNF4A CEP104 RAI1 LBR NGLY1 SAMD9 NME8 DDOST SUZ12 PEX1 SIK1 DGUOK RERE ALMS1 HDAC8 KCNQ2 SERPING1 IL21 PUF60 PTCH2 TYROBP FLVCR1 KRAS PROKR2 SNAI2 CSPP1 CCBE1 TSPYL1 PIK3CA FAH COLQ SLC6A9 CHEK2 IRAK1 AAAS STAG2 SOX10 TGM6 KIFBP ECE1 KCNQ3 HTT POLA1 FGFR2 SEC23B IRGM GATA6 CLTC ASAH1 ITGB4 NAB2 C1R PIBF1 TERT FOXC1 IRX5 BTK KCNB1 DCLRE1C CDKN2A FTL KNSTRN CBS CDON TCF3 RPL11 FLAD1 ZMPSTE24 MTM1 PACS1 PSEN1 DDIT3 TGFB1 STN1 IGF2 MEGF10 GABBR2 RIPK4 MYH7 PLA2G2A CCDC47 TCF4 SLC10A2 SLC25A1 MLH3 NOTCH1 AARS1 RRAS2 GPC4 HLA-DPA1 CHD7 RSPH3 PTS PEX16 EPRS1 DOCK8 GREM1 HPGD COX7B PIGN ND3 SMC1A SCN3A RIPK1 IDH1 B4GALNT1 SCN4A SUFU DDHD2 NPHS1 FOXF1 KLRC4 CCND1 DNAJC21 COG7 C9ORF72 WWOX TSC1 USP9X TRNK SMC1A MEN1 ASCL1 RNF43 AP2S1 JAK1 HMBS ADA2 RSPO2 CAVIN1 RNF43 RET CCR6 WASHC5 CHRNA1 HLA-B TP63 KRAS STAT4 SETD2 AMER1 VAMP1 TMEM216 TJP2 BMPR1A ZNF423 ARVCF NFKBIA ATRX NFKB1 PMS1 IQSEC2 MSR1 PGAP2 RECQL4 MSH2 MKS1 POGZ F12 GRM1 CACNA1A FUS JAK2 ATRX POLG KLHL7 RECQL4 NCF2 WHCR PLXND1 ALS2 MAP3K7 JAK2 CCDC103 SLC9A6 CEP120 CDCA7 CDKN2A RET AP3B2 CACNA1A CLCA4 AGGF1 MRPS28 MUTYH HRAS FGFR1 DNAH11 SAR1B FLNA FCGR2C ATXN3 TRIM28 CHEK2 RAC2 DLG3 CD79B KDM6A UBB HPCA ALDH18A1 NCF4 SLC25A13 BRCA2 BAX RPS6KA3 PPM1D MAP2K2 EDN3 MKKS EDN3 GLRA1 MCFD2 CAV1 IGH LRRK2 FGG MSH3 IL10 COX3 SMPD1 GJB1 SNAI2 NLRC4 ATP13A2 PAX4 PIK3C2A FGF8 SLC19A3 EP300 PIK3CA EFTUD2 NDUFB11 KIT VAC14 PLVAP NDUFS3 SH3KBP1 FOXH1 ATXN3 ITGB3 GRM7 SRP54 L1CAM TDGF1 IL2RA IARS2 STAT3 ERCC6 F11 SYT14 SLC30A10 PLA2G4A BAAT ZIC2 CHRM3 RAD51D ADCY6 GBA GREB1L NPHP3 CREBBP DHDDS OPTN WIPF1 NEXMIF PIK3CA MAP2K2 HNF4A FAS DYNC2I1 PANK2 TGIF1 FLNA OSGEP BBS1 HNRNPU PALB2 GTF2IRD1 DACT1 LAGE3 PNLIP ELN SLC5A7 CBLIF NUS1 KCNA2 CHAT MYLK EP300 TP53RK ADAT3 SMC3 STAG1 STAT4 SLC29A3 ADA2 ATXN8OS FOXE1 ITGB4 GBA TCOF1 MYH11 FBN2 VPS13A AGTR2 RTEL1 MAD2L2 SZT2 GDNF ALG13 RPGRIP1L EP300 RFWD3 SLC6A5 TLR4 LRRC6 PORCN STUB1 EDN3 PDGFRA NOP56 DICER1 MED12 DNAI1 PEX16 NEK9 CTBP1 TBCD ELANE CXCR4 RAD50 TNFRSF1A BRCA2 ERCC4 MYH8 CHRNA3 ATXN8OS C4A DCHS1 PDE8B ARHGAP29 KANSL1 MMP1 ALG8 FMR1 F13A1 ELN KLHL7 SLC9A7 ENG SETBP1 TET2 SDHC MVK TRAPPC11 FGFR2 TUBB4A LMOD3 ELP1 ERLIN2 SALL4 RRM2B POLR2A GFI1 MECP2 SLC46A1 DDC MCEE HOXB1 TBL2 STK11 RAD51 SLC7A7 MED12 CDKN2B WT1 SRCAP RET PDGFRL JAK3 DMPK ZNF81 NECTIN1 AICDA PLOD1 RPS28 PMS1 AKT1 PRDM16 IDS NBN GCK STAT1 DISP1 TRNE CDC45 KCNA2 ARX COL7A1 CD3E AXIN1 SHANK3 ECM1 LIMK1 CNKSR2 POLG SOX10 HLA-DRB1 EXT2 CFTR FGFR2 USP27X VANGL1 RAD51C HBB SYT1 PIGO ZBTB24 FGFR3 FANCI MITF ABCC6 SALL1 DNAAF2 NOTCH2 EMC1 ZIC3 DAXX EXOSC9 SYNJ1 SPG7 NPHP3 CAMK2B ATP1A3 NPC1 TNFSF15 VAMP1 HLA-DPB1 TTC7A UPB1 WFS1 TP63 PIEZO2 SLC25A24 CTNNB1 GPC1 SOX2 ACTB HELLS DNAAF6 MLH3 GJB6 BARD1 OCRL GPR35 MASP2 CHCHD10 PSPH LRP2 MYC FCSK TUBB6 MSH3 RMRP FCGR2A PRKCD ASPA NEUROD1 ATXN8 FLCN SDHC ATP8B1 CYBA CTLA4 STS CXORF56 MNX1 FOXH1 GABRA2 TCF4 THOC6 IL12RB1 PDX1 TRAK1 SDHC PITX2 GAS1 SMO STAG2 COL13A1 BCOR TRNH NEB PTPN22 SLC46A1 HGSNAT HLA-B COL5A2 RFWD3 GNAO1 RPL15 NODAL HNF1A NUP214 GATA1 EFEMP2 NCF1 RPS15A KMT2A IL2RB DISP1 KLHL40 WRAP53 RBM10 PPP1R12A FGFR2 PITX2 WNT3 COL1A1 PYGM SEC23A ABCC2 BLM ACTA1 POLD1 RPS27 FASLG DMPK SLC6A8 PTEN PLP1 CARS2 PTF1A TDGF1 PPP2R3C NPHP1 GDI1 C12ORF65 FGF8 CCDC39 STXBP1 LAMC2 DDX6 ZIC3 MSH6 SCARB2 NOP10 PAX3 NR4A2 PSAP ACD LARGE1 HABP2 IL6 WDR73 VAMP1 ITGB3 NIPBL ITGA2 HYOU1 APC TARDBP SRPX2 EGFR PITX2 ACOX1 ATP1A3 RPL10 TTBK2 SPINT2 PGM3 RTEL1 WAC STAG2 STXBP1 APC PLEC FLNA DNM1 FLI1 TCIRG1 SMAD4 SCN4A PTPN3 PIK3CA CAMTA1 CHD7 FGFR2 HLA-B SPINK5 TGFBR2 HNF1A PLAA RBM8A CHRND CD55 TTC37 LONP1 TOP3A KIT ABCA3 STK36 RFX5 DPP9 TMEM231 PALB2 NRAS ARV1 DLX4 FREM1 PEX6 TGFBR1 ZMYND10 RRM2B TIMM8A REST ZIC2 WARS2 PTEN CTCF CTLA4 SLC2A3 ZIC2 EFL1 ECE1 KCNC3 PIK3R5 ITGA2B GPC3 SLC9A3 KCNQ1 NDUFAF3 HMGA2 AGA NEUROG3 MAPT MFF FOXP3 HNF1B ASCC1 SPIB PTEN FANCB DMP1 DNM1L ENPP1 DNAH1 TNXB AKT1 KEAP1 INS ACADVL DISP1 PTCH1 CDKN1C LEMD3 TPM3 GLI2 GLI2 MCIDAS SLC6A3 EPCAM IVNS1ABP ATP1A3 NSUN2 JUP ATP7B CHST14 IL23R NDUFA6 PTPN12 CHRM3 CFAP300 SLC25A4 DHODH CTC1 ABCB1 DHCR7 BMPR1A CHD4 FAM13A POLR3A IFNGR1 STK11 OPLAH AK2 TBX3 CHAT ARX TUBB4A GNAQ MYCN KRAS HFE SH2B1 CD3G CYP27A1 SLC18A3 NODAL DACT1 TEK HOXD13 B3GALT6 RPL5 SLC39A4 KIF1A STAT5B GDNF RTTN SMAD4 CDK19 PEX10 COG4 RHBDF2 SPEF2 RREB1 CEP57 RAD51C MLX DLL4 CEP41 TBX1 PIGT RNASEH1 JAK2 GEMIN4 RFXAP GCH1 ERMARD SPG11 KIAA0586 CDH11 GPIHBP1 MAPT SPG7 ZSWIM6 FLNA RELA GCDH KLHL41 NUP88 AFF4 SPG21 KAT6B SMAD4 TBP RPS7 MMP21 PTRH2 EDN3 PIGL SPP1 SOD1 ZFPM2 REPS1 KAT6B MUTYH CISD2 BRIP1 PTCH1 NUP133 GDNF AR IGLL1 PRKCD PTCH1 POMT1 TXN2 SLC18A3 CHRNE PORCN TK2 MACF1 SLCO2A1 CHRNE FAH RAI1 XIAP PI4KA BRCA2 ARID2 HDAC8 EPCAM CDC6 TDGF1 DVL3 MATR3 ABCB4 UBA5 BMPR1A ATM SHROOM4 COL5A1 ATRX POLG2 GDF6 SERPING1 SOX2 TGIF1 UBR1 POLG2 ACTA1 PIGN ERLIN2 BCOR CSPP1 TERT ARFGEF2 IKZF1 UBE2T MUSK GFPT1 VPS51 HCCS BDNF HMGA2 TTC7A LTBP4 SKI RPS20 RUNX1 TTC12 DCC MSH2 RPS24 WT1 INPP5E FKTN NDUFS2 TFAP2A RPL35 SLC2A10 RPS17 COMT ITGA6 INPP5E CDC73 NEB SBDS MYH3 BRAF PIGV SETX LAMB3 PIEZO2 MAPT KCNQ1OT1 PTCH1 UBA5 PHKA2 POU2AF1 FOXH1 CCDC28B TREM2 GP1BB VAPB ABCC8 MBTPS2 FLII PHKG2 SALL1 ARPC1B SP110 TCTN2 MUTYH STN1 FANCA NEFH ATXN3 POLG RPL31 DLL1 WNT4 HFE CCN2 SHH RET DLC1 SDHB EP300 SOX10 ATP7A MSH6 ALS2 C2CD3 FGFR1 SIN3A HLA-DQB1 SRP54 CCNQ TINF2 BUB1 CACNA1G SMAD4 SHPK POMT2 DHCR24 ARID1B WAS NEK10 MAPK1 PABPN1 MYOT SOX5 ATP6V1A PQBP1 BIN1 PSTPIP1 COL7A1 SYT2 TWIST2 ACTB DOCK6 EDN3 QDPR PIK3CA IGF2 H19-ICR B3GLCT DLL1 CCR1 MYCN SAR1B COQ2 COX4I2 ERGIC1 FH HIRA TNFSF12 PIK3R1 RELA MITF F5 GMPPA EPHX1 CTNNB1 KIAA0319L TLR2 TGFB1 CDKN1B LIPA SSR4 COQ4 TPM3 PRPH ARX DACT1 MKS1 HLA-DRB1 PYCR1 SH2B1 ZIC2 TBX3 NONO FAT4 MID2 COL5A1 PRKAR1A ZNF41 MSH2 POLG DLL4 UBTF ERCC8 CTHRC1 GBA2 COL7A1 NUP62 FANCB FTL SIX3 SALL4 SDHC GJB2 LIG4 ACTL6B MDM2 LAMA3 MYO5B MTOR ALS2 CDON DGAT1 KAT6A ALG3 TAF1 SERPING1 SYT1 BMPR1A PAK1 SI TWIST2 LRP5 RNF125 TPM2 PTEN DYNC2I2 CTNNB1 SNRPB SLX4 KY ACTA1 FGF8 HCFC1 PKD1 XRCC4 TRIP13 CDC73 MECP2 ELN CFTR NOTCH3 NECTIN1 KMT2D DIS3L2 PPP2R5D SYT14 SLC44A1 TRNL1 KLHL41 WNT3 RYR1 JMJD1C ODAD1 CREBBP CCR6 HYLS1 SETX COX2 BRCA2 KIAA0586 SIX3 ORC1 GTF2I POT1 ABCB11 AURKA VWF DCTN1 IRF2BPL KIF3B ATXN8 MFF SETD5 ATP6 TWNK TAF1 IGHM LAMB2 EDNRB KLHL41 TCF4 NALCN MBTPS2 GATA1 OTX2 DOK7 SCN3A MPI VPS33A GDF3 RET OTC SEC23B APC PEX2 TET2 SETBP1 PMS2 DSP POLR1C SIX3 CYFIP2 FKRP GLA AP1S1 ACTA1 HYDIN RPL35A RET FGG SHH MNX1 MECP2 DSE ND6 PSAP HLA-B TRMT10C KIT RFX6 B3GLCT ATXN2 MYORG CPOX ITCH SPAG1 LMNB1 TSPYL1 TWNK FREM1 DLL1 ATXN7 SLC2A2 SAA1 ARHGEF6 TEK ABCC6 CHMP2B SLC19A2 TRNS1 CDON KLHL40 NCAPG2 COL14A1 CLMP YY1 RPL11 LINGO1 AHI1 MSX1 MECP2 FGFR1 CREBBP NDUFAF2 TBX4 RFXANK OPA1 RARB GBA HBB MBTPS2 ERBB2 FGB GATA6 WFS1 ND4 CDKL5 TBCE GBA NDUFA9 NAA10 ATP7A F5 FAS DCHS1 TSPAN7 FLVCR1 PLCG2 GRIN2D MS4A1 SPINK1 UBQLN2 ATP11A PUS3 PYROXD1 KIT NEFH MYOD1 VAC14 BUB1B ATRX LIPA TRAPPC11 TBK1 FOXJ1 CDH1 ITGB2 TWNK RPL10 ATP7A LCT CYBC1 CNTNAP2 JAK3 CD109 XRCC1 ZC4H2 PCGF2 CHRND SLC1A2 IRF5 PTCH1 DLL1 LMX1B ASAH1 TK2 GAS1 CNTNAP1 FGA DYNC2H1 FRAS1 TCF4 NEU1 HESX1 GP1BA FANCL BTNL2 NEXMIF PGAP3 NOP10 PLEC RPS29 KIF23 MECP2 TGIF1 PLA2G6 TYMP PTCHD1 HSPA9 TECPR2 PIGA MEIS2 FIG4 CDK4 ACVRL1 POLG DDX59 MSL3 FBXO7 GP1BB CAV1 MAP3K7 MAPT PIGY KLF11 FARSB SNCAIP SALL4 PACS1 GLI2 AHI1 FUZ PEX14 SRP54 TNFSF12 IGHM CRKL IL10RA SCN9A BCL10 RPS26 GLI3 SDHA RBPJ AFG3L2 TRMT5 DNAL1 FLNA RB1 MLH1 GMPPA KIT SPART GIGYF2 AXIN2 POLR3A HSD3B7 DYRK1A IL12A-AS1 RECQL4 EXOC6B MKKS CDKN1B KIFBP GRHL2 TP53 PFN1 DDHD2 PAK3 ACTG2 SDHB ITGB4 FA2H RNF6 ZAP70 TMEM138 ADNP DNMT3B PERCC1 COL7A1 SLC5A7 SCO2 CFAP221 C11ORF95 GP1BA CD96 PANK2 KCND3 MCOLN1 NEPRO SMAD7 SLC52A3 PRSS1 CLIP2 FANCF SFTPC POR PRKCSH ODC1 CEP120 BAZ1B GYS2 DNAAF3 GAS2L2 MTTP TPM3 IL1RN STOX1 ICOS SIX3 EBF3 XRCC2 CDKN2C SLC6A3 STX1A SIX1 ATRX FGF12 EP300 GRIN2D POU6F2 SFTPA2 ITGA2B ATXN7 DLG1 MIR17HG B9D1 CDON ADGRG1 ASXL1 CDKN2B B2M NHP2 KMT2A AMACR CCDC22 MAGEL2 TBC1D24 INSR PARN MAP1B NPC2 PARS2 BLNK DIS3L2 MED12L CORIN PDP1 TNXB MYPN ZIC2 FGA ALDH18A1 AHCY GUCY2C ACOX1 PRSS2 ALS2 NONO IFT80 EXT2 CLMP CLCN4 MEN1 MYMK PARN VPS35 NOD2 TP53 NUTM2B-AS1 CDK4 ACTA1 HBB GABRD TGFBR2 APC BRCA1 KCNAB2 CRLF1 USF3 RAPSN NOTCH1 H19 HDAC4 AMACR UROD ND5 PTCH1 LAMB3 NCF2 CR2 HRAS CDH1 TNPO3 F5 AGRN RFXANK SDHD MEFV ODAD3 NDUFB11 CYBC1 SNAP25 SHH HSD3B7 FIG4 WNK1 TREX1 ELP1 POLE TWNK ASXL1 GLI2 SLC25A13 PNP TMPRSS6 BACH2 SRSF2 SDHB FOXG1 FGFR3 GATA6 CASP10 CTC1 KITLG TBX1 RFX5 ENPP1 PIK3CA FAS AFG3L2 BMPR1A CCNQ CNTNAP1 SLC6A19 SKI COG6 TERC CBL ADAMTS3 EDNRB YWHAG COG8 KCNK9 ODAD2 DVL3 TGFBR2 SOX10 CNKSR2 TMEM237 CDH1 SEMA4A SLC37A4 VPS13A NGLY1 ACOX2 PIEZO2 CYBA PPP2R5D PIEZO1 SDHB STUB1 TERT NHP2 SEC63 FRG1 DZIP1L TRNW RTEL1 PEX5 SDHD CCND1 PCNA KRT8 FRAS1 MLH1 ITCH YARS2 WDR73 FLCN DLEC1 ADAMTS3 ND6 MYO9A MYO5B DNAAF1 ATXN1 TGFB1 TMEM237 FGFRL1 IL1RAPL1 RFXAP KCNK9 MTMR14 ND2 POLG IL12B CREBBP HTT APC DISP1 CHAMP1 TERT AAAS MC1R RPS10 NTNG1 KDM3B NODAL PLG ADAM17 ATP6 ARNT2 SMO CHRNA1 MRE11 RSPH9 TERC CFAP298 ACTA2 SKIV2L IQSEC2 C19ORF12 IRF6 TRAPPC12 GNAS PMS2 MSX1 LMAN1 ZEB2 EFL1 GNS
Protein Mutations 2
C10D V30M
HP:0001638: Cardiomyopathy
Genes 744
RAB3GAP2 LMNA ND4 LAMA4 TRNT NDUFA10 TRNL1 TNNT2 MMUT PEX5 NDUFS6 PEX11B COL7A1 LDB3 RAF1 MYBPC3 PPCS LAMA4 GNPTAB MYO18B LIMK1 GSN ERCC8 POMT1 COL7A1 PPARG PDGFRA AGK NDUFA2 HBB HADHA COA5 GATA4 LAMA3 FANCI GMPPB TNNI3 MYH7 TARS1 CAV3 FOXRED1 TTR EYA4 MYL3 HJV ELAC2 TMEM43 MAP3K20 SYNE2 RIT1 TPM2 MTO1 FBXL4 TMEM43 ATP5F1D SLX4 VHL JUP POMK TNNT2 ACTA1 RYR2 GPC3 KCNH1 PSEN1 TCAP CDH23 EMD DSP ELN WARS2 KLF1 GTF2E2 TNNT2 NF1 LDB3 TRNL1 RAD51 RYR1 TRNT1 VPS33A ERCC4 POLG LMNA SLC25A4 ABCC9 ACTN2 FHL1 LMNA COX2 SLC25A20 TXNRD2 SDHA TNNI3 GTF2I CRYAB ATP6 FLNC SCN5A FHL1 GLB1 FANCL NDUFA1 NDUFA11 LMNA CAVIN1 PLN AGL NDUFAF4 ACAD8 NAGLU GUSB DLD ATP6 AIP TWNK NAGA PET100 RNU4ATAC TPM3 GTPBP3 SLC25A4 FKRP XYLT2 FHL1 EPG5 BRAF PEX2 DSG2 PLN MAP2K1 HJV BRAF TRNH NEB HADHB MRAP POMGNT1 HGSNAT VPS33A SCO1 FKRP IDUA TPM2 TTR NDUFV2 EPG5 TSFM DSP MIPEP GLA BRAF POMT1 FANCE SDHD CSRP3 GPC4 PRKAG2 ND6 TMEM70 UQCRFS1 NDUFV1 AIP CPT1A ALMS1 PYGM COA6 ACTA1 RERE ACTA1 BAG3 PRDM16 RBCK1 FANCM NF1 TWNK IDUA NDUFAF3 TNNC1 NDUFS4 COX14 ACAD8 TAF1A NBAS SLC2A10 UBR1 MYOT ABCC6 NDUFA13 LIPT1 SLC19A2 PPP1CB ATAD3A TRNS2 MYOT FTO TRNS1 PRKAG2 OPA1 NEU1 COQ2 SGCB MAP2K1 SLC25A3 SDHA CAV1 IFIH1 PLN MRPL44 ANKRD11 SURF1 MEN1 GATAD1 STAR ND3 TACO1 ND1 GNE SCN5A NEB GBE1 ATP5F1E LMNA LDB3 GNPTAB HBB MYBPC3 FANCG FXN WFS1 ND4 TMEM126B ACADS ND5 RAF1 NEXN DES NDUFAF1 MYOCD ATPAF2 PCCB MYPN KIF20A EYA4 COX6B1 RAF1 COX1 LMNA PCCA SDHA TPI1 LAMA2 MYH7 TRNV LMNA PEX14 GMPPB NPPA NDUFA6 PKP2 VCP RNASEH2C ALMS1 VAC14 TIMMDC1 NDUFA10 HFE BCS1L BAG3 TRNK SPTA1 SHOC2 NDUFS7 ACTC1 TWNK GATA5 LMNA TOP3A LMNA SELENON RAF1 MYL2 TPM1 PALB2 SURF1 TPM1 FHL2 MYH7 TPM2 PSEN2 SGCD TAZ SYNE1 WARS2 TNNI3 MIB1 MTFMT SGCD TERT GTPBP3 NDUFS3 HMGCL NDUFA11 TRIP4 MYSM1 KCNJ8 GPC3 HSD17B10 KCNQ1 TTN NDUFAF3 PEX16 RNASEH2B TRNF FKTN ANK1 NDUFB11 ACTN2 NDUFA12 NDUFA9 CPT2 TGFB3 ND2 FANCB ANKS6 BAG3 BRAF XK HADHA FLAD1 SGCB IDH2 MYH7 FKTN NDUFA4 TMEM126A BBS2 TCAP MYH6 FIG4 FHL1 NNT POMT1 ACADVL DMD NUBPL POLG SAMHD1 RBM20 ACTC1 NDUFB11 ATAD3A CDKN1C ERBB3 SDHA DSC2 MYPN MYH7 NDUFV2 NUP107 JUP GPC4 EPB42 GATAD1 SHOC2 ADCY5 MYOZ2 BOLA3 DSG2 SLC25A4 C1QBP SELENON COX15 CLPB NDUFA2 PEX7 COX7B PSEN2 SLC22A5 ND3 FKTN MC2R AGPAT2 TRNN KRAS MRPL3 TNNT2 FOS KRAS PCCA PHYH HFE ANO5 PEX7 ABCC9 USP9X HAND2 TRNK RBM20 NDUFB3 COA3 DMD NDUFAF6 USP8 PRKAG2 CHKB DPM3 PARS2 TNNI3 HLA-B BSCL2 HAMP NDUFV1 PNPLA2 SCO2 JUP NDUFS1 ATP5MD NDUFS7 IDUA RAD51C TRNL1 LIMS2 MLX DES ABCC6 CLIP2 PIGT PIGT RNASEH1 FLNC ALG1 DSP NDUFS2 AHCY FANCF RAF1 ADCY5 NRAS POLG COX7B VCL POMT2 NDUFS8 TTN TNNC1 FXN BAZ1B HNRNPA1 SLC25A20 LAMC2 SDHD NDUFS2 COX20 D2HGDH SLC25A4 ADAR MMUT KLHL41 FANCD2 PYGL HCCS JPH2 RMND1 AGK GMPPB TPM3 ACTC1 TRNQ RRM2B LIAS RFC2 ALG1 HPS1 PTPN11 SPEG PMM2 XRCC2 TMEM70 ND1 SGSH FASTKD2 DCAF8 TANGO2 TNNI3 PSEN1 MYBPC3 DOLK NDUFS3 MYH6 TRNS1 SPTB MLYCD NDUFAF2 TNNI3K MYPN HRAS MRPS22 VCL ANKRD1 CPT2 TKFC BRIP1 GYS1 MYL2 ERCC3 PTPN11 PPCS PEX19 SCO2 TTPA PDHA1 TAPT1 NEXN INSR POMT1 MYH7 MYH6 MAP2K2 ABHD5 LDB3 DES TK2 FLNC FAH NDUFS8 MAP2K1 MYPN NDUFAF4 HACD1 FOXRED1 MPLKIP AHCY ATP6V1A SUFU COX3 MGME1 BMP2 NDUFAF5 TNNI3 HADHB QRSL1 SLC4A1 NDUFB10 ND1 ECHS1 PEX13 NDUFS4 NAXD NDUFS4 ACADL COX8A NAGA ACTA1 GABRD DNAJC19 POLG2 TAZ ACAD9 BRCA1 SLC25A3 NDUFB11 KCNAB2 AIP NDUFB8 SDHA FANCC DPM3 FKTN WFS1 KRAS COA8 ND5 PEX1 PEX12 FOXRED1 HRAS SDHAF1 DES UBE2T VCL CSRP3 BRCC3 HADH ARSB ERCC6 HCCS NDUFB11 SLC30A10 FIG4 LMNA DMD COX10 MGME1 CPT2 TMPO TKFC TWNK CRYAB LMNA SKI PRDM16 NDUFS1 SOS1 NUP107 TNNT2 PEX3 MAP2K2 NDUFS2 SLC19A3 ACAD9 RNASEH2A NDUFV2 KBTBD13 ENPP1 GTF2IRD1 PPA2 DOLK LAMB3 KCNQ1OT1 NDUFAF8 CSRP3 HADHA ERCC2 NDUFS8 DTNA COG7 MRPS14 XYLT1 CAP2 AGPAT2 DSP SLC40A1 FKRP TGFB1 PTPN11 TTN HADH POMT2 SDHAF1 NDUFS2 LAMP2 VPS13A NDUFAF5 HAMP XRCC4 FANCA MYH7 PMM2 MAD2L2 ATAD3A COX15 TACO1 CLN3 PET100 TMEM126B RFWD3 POLG MYH6 DSG2 PEX26 ABCC9 TRNW PEX6 TRNW DMD HNRNPA2B1 MYPN TREX1 LTBP4 TRNK YARS2 PNPLA2 ITGA7 AARS2 BRCA2 ND6 CENPE PEX7 DMD CRYAB INSR TNNC1 TPM1 ND2 POLG IL12B MMP1 HADHA PCCB NDUFAF2 TXNRD2 LAMP2 NDUFAF1 SGCA MICOS13 PHYH NEXN NEK8 BSCL2 CISD2 RRM2B RNF113A NEBL IGF2 MEFV H19-ICR TBL2 KAT6B SMC1A NDUFB9 JUP SARDH GSN TFR2 CPT2 DMPK PEX10 DLD SYNE2 TPM3 GPR101 GATC GTF2H5 COA8 DNAJC19 DSP RMRP MYLK2 ACADVL PGM1 TTN COQ4 PRDM16 PPARG RNU4ATAC CRYAB ITPA GJA5 GNS TAZ GYG1 TRNE SDHB
HP:0001635: Congestive heart failure
Genes 261
TBX20 RAB3GAP2 AGPAT2 FLNC LDB3 TMEM127 FOS COG7 PHYH HFE PRKAR1A GNPTAB KCNJ5 LIMK1 TRNK RBM20 PPARG SDHAF2 HBB STAT1 HADHA VHL FGFR3 PRKAG2 ENPP1 RET CAV3 SELENON EYA4 PNPLA2 PRKAR1A SCO2 LMNA RYR1 FBN1 MYL3 HJV ELAC2 TMEM43 TRNL1 CITED2 DES ABCC6 CLIP2 COX3 CYTB JUP TPI1 ADCY5 PSEN1 FH GDF2 DSP ELN TTN IKBKG GJA1 BAZ1B HNRNPA1 GPR35 COL1A1 CCR6 TRNQ AFF4 RFC2 GTF2I TTN GATA4 CACNA1S GLB1 TNNI3 AGGF1 SF3B1 CAVIN1 PLN TRNF TNNI3K TCF4 VCL TUBB RET ATXN7 LMNA LMNA GTPBP3 XYLT2 SDHB FBLN5 HBA1 MYH7 TMEM127 KIF1B DES HADHB DNMT3A VPS33A CAV1 CDH23 TLL1 EPG5 ATP6V1A GLA BMP2 EFEMP2 SLC25A11 HADHB ACTN2 ND1 PSMB8 SCN1B CP TMEM70 MYD88 HBB SMAD4 ALMS1 MTTP MAX ACAD9 VHL SLC25A3 FGD1 NDUFB8 TRNW HBA2 SDHD BCHE WRN SLC2A10 TRNS2 CYTB ENG SDHB NDUFB11 LMNA DMD COX2 CAV1 NKX2-5 LMNA SURF1 HLA-DRB1 GATAD1 SDHC PRKAR1A TRNK PRDM16 TNNT2 GNA11 IFIH1 ABCC6 HBB MDH2 NDUFS2 TRNV SDHA ACAD9 FXN SLC25A26 SLC19A2 GTF2IRD1 RPS19 GLA PPA2 MYPN EYA4 CITED2 DTNA MAX NF1 LMNA XYLT1 ND6 SNAP29 TBX20 DSP MST1 FLNA DLST MYH7 MYH7 ADAMTSL2 MYH7 VCP SCN4A ALMS1 NKX2-5 GDNF HFE TF MECP2 BAG3 HAMP TRNK TET2 ACTC1 RASA1 LMNA LMNA MYH6 TRPM4 TRIM37 SDHD TLL1 TRNC STRADA CCN2 HNRNPA2B1 MYH7 TAZ RET CLIC2 SGCD GTPBP3 PEX7 SDHB TRIP4 MYSM1 TPM1 NDUFAF3 PTEN CEP19 SDHD NDUFAF1 FGF23 EPAS1 ND5 SLC17A5 HADHA GATA6 BSCL2 ATP5F1A ACVRL1 CLIC2 IRF5 ACTC1 TBL2 MAPRE2 JUP CASR KIF1B VHL NSMCE2 TRNL1 ADCY5 DNAJC19 DSP MYLK2 PLOD1 COX1 MYH6 COL1A2 IDS PPARG ENG SCN5A GBA TRNS1 PSEN2 SLC22A5 TRNE
SNP 0