SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT03423186

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

An Open, Non-controlled, Parallel, Ascending Multiple-dose, Multicenter Study to Assess Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of SOBI003 in Pediatric MPS IIIA Patients

MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS IIIA is characterized by devastating neurodegeneration with initially mild somatic involvement. The aims of the present study is to assess the dose related safety, tolerability, PK and PD of SOBI003, a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).

NCT03423186 Sanfilippo Syndrome Type A (MPS IIIA)
MeSH:Mucopolysaccharidosis III

1 Interventions

Name: SOBI003

Description: Weekly i.v.infusion
Type: Drug
Group Labels: 3

Dose group 1 Dose group 2 Dose group 3


Primary Outcomes

Measure: Safety will be measured by adverse events frequencies (by type and severity)

Time: Week 24

Secondary Outcomes

Measure: The observed serum concentration immediately before the start of infusion of SOBI003 (CPre-dose)

Time: Weeks 1, 2, 3, 4, 5, 8, 12, and 24

Measure: The observed serum concentration at the end of infusion of SOBI003 (CEnd of inf)

Time: Weeks 1, 2, 3, 4, 8, 12, and 24

Measure: The time of the end of the infusion of SOBI003 (tEnd of inf)

Time: Weeks 1, 2, 3, 4, 8, 12, and 24

Measure: The maximum observed serum concentration (Cmax)

Time: Weeks 1, 4, 12, and 24

Measure: The time at which the maximum serum concentration is observed (tmax)

Time: Weeks 1, 4, 12, and 24

Measure: The minimum observed serum concentration (CTrough)

Time: Weeks 1, 4, 12, and 24

Measure: Clearance (CL)

Time: Weeks 1, 4, 12, and 24

Measure: The area under the plasma concentration-time curve from time 0 to last sample (AUC0-168h)

Time: Weeks 1, 4, 12, and 24

Measure: The half-life (t1/2)

Time: Weeks 1, 4, 12, and 24

Measure: SOBI003 concentration in cerebrospinal fluid

Time: Weeks 12 and 24

Measure: Proportion of patients having anti-drug antibodies in serum

Time: Weeks 2,4,8,12 and 24

Measure: Proportion of patients having anti-drug antibodies in cerebrospinal fluid

Time: Weeks 2,4,8,12 and 24

Measure: Change from baseline in Heparan Sulfate levels in cerebrospinal fluid

Time: Weeks 12 and 24

Measure: Change from baseline in Heparan sulfate levels in serum

Time: Weeks 2, 3, 4, 8, 12 and 24

Measure: Change from baseline in Heparan sulfate levels in urine

Time: Weeks 2, 3, 4, 8, 12 and 24

Description: Quotient between age equivalent score and age, 0 - 100%, where high values are desirable. The age equivalent score represent the age of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development.

Measure: Change from baseline in Neurocognitive Development Quotient

Time: Week 24

Description: The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development.

Measure: Change from baseline in Age-equivalence score as assessed by BSID-III or KABC-II

Time: Week 24

Description: The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II). The Vineland is designed to measure adaptive behavior of individuals from birth to age 90. The Vineland-II contains 5 domains each with 2-3 subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior.

Measure: Change from baseline in Age-equivalence score as assessed by VABS-II

Time: Week 24

Description: Grey matter contains most of the brain's neuronal cell bodies. The grey matter includes regions of the brain involved in muscle control, and sensory perception such as seeing and hearing, memory, emotions, speech, decision making, and self-control. The gray matter volume will be measured by volumetric magnetic resonance imaging (MRI).

Measure: Change from baseline in gray matter volume

Time: Week 24

Description: Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. Lower scores indicate better functioning. Min score = 0, and max score = 144.

Measure: Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) total score

Time: Week 24

Description: Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning.

Measure: Change from baseline in PedsQL™ Family Impact Module total score

Time: Week 24

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 S298P

At least one S298P mutation in the SGSH gene 2. Contraindications for anesthetic procedures, surgical procedure (venous access port) MRI scans and/or lumbar punctures 3. History of poorly controlled seizures 4. Patients is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results 5. Significant non-MPS IIIA-related CNS impairment or behavioral disturbances, which in the investigator's opinion, would confound the scientific integrity or interpretation of study assessments 6. Prior administration of stem cell or gene therapy, or ERT for MPS IIIA 7. Concurrent or prior (within 30 days of enrolment into this study) participation in a study involving invasive procedures Inclusion Criteria: 1. Informed consent obtained from the patient's legally authorized representative(s) 2. Patients with MPS IIIA, as confirmed by both: - A documented deficiency in sulfamidase enzyme activity in concordance with a diagnosis of MPS IIIA, and - Normal enzyme activity level of at least one other sulfatase measured in leukocytes 3. Chronological age of ≥12 and ≤72 months (i.e., 1 to 6 years) at the time of the first SOBI003 infusion and a developmental age ≥12 months at screening as assessed by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) 4. Medically stable patient who is expected to be able to comply with study procedures Exclusion Criteria: 1. --- S298P ---

At least one S298P mutation in the SGSH gene 2. Contraindications for anesthetic procedures, surgical procedure (venous access port) MRI scans and/or lumbar punctures 3. History of poorly controlled seizures 4. Patients is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results 5. Significant non-MPS IIIA-related CNS impairment or behavioral disturbances, which in the investigator's opinion, would confound the scientific integrity or interpretation of study assessments 6. Prior administration of stem cell or gene therapy, or ERT for MPS IIIA 7. Concurrent or prior (within 30 days of enrolment into this study) participation in a study involving invasive procedures Sanfilippo Syndrome Type A (MPS IIIA) Mucopolysaccharidosis III This is an open-label, non-controlled, parallel, sequential ascending multiple-dose, multicenter study to assess the dose related safety, tolerability, PK and PD of SOBI003 in pediatric MPS IIIA patients. --- S298P ---



HPO Nodes