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Report for Clinical Trial NCT03417830

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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 Amyloidosis
MeSH:Amyloidosis
HPO:Amyloidosis

3 Interventions

Name: GSK2315698 (CPHPC)

Description: GSK2315698 will be administered as 20 milligrams per hour (20 mg/hour) IV infusion (in the vein) for up to 72 hours followed by 60 milligrams (mg) three times daily as SC injection for 8 days. Dose level and frequency will be adjusted according to renal function.
Type: Drug
Group Labels: 2

Subjects with ATTR-CM in Part A Subjects with ATTR-CM in Part B

Name: GSK2398852 (unlabeled anti-SAP mAb)

Description: Subjects will be administered up to 490 mg of GSK2398852, IV. Dose level will be adjusted based on emerging imaging data.
Type: Drug
Group Labels: 2

Subjects with ATTR-CM in Part A Subjects with ATTR-CM in Part B

Name: 89Zr-GSK2398852 (89Zr-labeled anti-SAP mAb)

Description: 89Zr-GSK2398852 will be available as solution containing 10 mg 89Zr-GSK2398852 for Infusion. Subjects will be administered 37 (Megabecquerel) MBq radioactive dose of 89Zr-GSK2398852 by the IV route at each dosing session.
Type: Drug
Group Labels: 2

Subjects with ATTR-CM in Part A Subjects with ATTR-CM in Part B


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

Purpose: Diagnostic

Allocation: Non-Randomized

Sequential Assignment


There is one SNP

SNPs


1 V30M

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 ---



HPO Nodes


HPO: