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Report for Clinical Trial NCT02060526

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of rhHNS (Recombinant Human Heparan N Sulfatase) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Early Stage Mucopolysaccharidosis Type IIIA Disease

Sanfilippo syndrome Type A, or Mucopolysaccharidosis (MPS) IIIA, is a rare lysosomal storage disease caused by deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, there is an accumulation of the glycosaminoglycan, heparan sulfate, resulting in progressive neurodegeneration. Symptoms are usually first noted in the 1st or 2nd year of life, although definitive diagnosis is often delayed, with an average age of diagnosis of 4.5 years. The disease is characterized by developmental delays initially, followed by neurological developmental arrest, then regression. These developmental deficits are typically associated with severe behavioral disturbances. Patients have a significantly reduced lifespan, with few surviving beyond the 2nd or 3rd decade. The purpose of this study is to evaluate the safety and efficacy of recombinant human heparan-N-sulfatase (rhHNS) in pediatric patients with Early Stage Mucopolysaccharidosis Type III A Disease.

NCT02060526 Sanfilippo Syndrome
MeSH: Mucopolysaccharidosis III Syndrome

1 Interventions

Name: Recombinant human heparan N-sulfatase [rhHNS]

Description: Recombinant human heparan N-sulfatase [rhHNS]

Type: Drug

45 mg Q2W 45 mg Q4W Placebo


Primary Outcomes

Description: The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which was computed as a ratio and expressed as a percentage using the age equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). The BSID--III DQ score is based on the cognitive domain. A positive value indicates improvement in health and cognition. Overall response was the maximum decline in the DQ of 10 points or less over 48 weeks. Number of participants with the overall response were reported here.

Measure: Number of Participants With Overall Response Using Bayley Scales of Infant Development Assessment Third Edition (BSID-III)

Time: Baseline (Week 0) up to Week 48

Secondary Outcomes

Description: An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product related. This included an exacerbation of a pre-existing condition. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Measure: Number of Participants With Serious Adverse Events (SAE)

Time: Baseline (Week 0) up to Week 52

Description: An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product related. This included an exacerbation of a pre-existing condition. TEAEs were defined as AE occurring on or after the time of first IDDD implantation or LP procedure to the end of study (EOS) visit (+30 days).

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

Time: Baseline (Week 0) up to Week 52

Description: A participant was considered positive if they had at least 1 positive result during the study. Once a participant reported antibody positive, they were considered positive for the remainder of the study.

Measure: Number of Participants With Positive Anti-recombinant Human Heparan-N-Sulfatase (rhHNS) Antibody in Serum at Week 48

Time: Baseline (Week 0) up to Week 48

Description: The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0, 100). The overall DQ score is calculated from the mean age-equivalent score obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). A positive value indicates improvement in health and cognition.

Measure: Change From Baseline in Vineland Adaptive Behavior Scales Second Edition (VABS-II) Development Quotient (DQ) Score at Week 48

Time: Baseline (Week 0), Week 48

Description: The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The DQ is a means to express a neurodevelopmental/cognitive delay which was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). The BSID--III DQ score is based on the cognitive domain. A positive value indicates improvement in health and cognition.

Measure: Change From Baseline in Development Quotient (DQ) Using Bayley Scales of Infant Development Assessment Third Edition (BSID-III) at Week 48

Time: Baseline (Week 0), Week 48

Description: The change from baseline in grey matter volume at Week 48 was assessed by magnetic resonance imaging (MRI).

Measure: Change From Baseline in Total Cortical Grey Matter Volume at Week 48

Time: Baseline (Week 0), Week 48

Description: Change from baseline in concentration of GAG in CSF at Week 48 was reported.

Measure: Change From Baseline in Concentration of Glycosaminoglycan (GAG) in Cerebrospinal Fluid (CSF) at Week 48

Time: Baseline (Week 0), Week 48

Description: The concentration of GAG in urine was normalized to the urine creatinine value and reported as milligram (mg) GAG per millimole (mmol) creatinine.

Measure: Change From Baseline in Concentration of GAG in Urine at Week 48

Time: Baseline (Week 0), Week 48

Description: Concentration of rhHNS in CSF was assessed using validated enzyme-linked immunosorbent assay (ELISA) method.

Measure: Concentration of Recombinant Human Heparan-N-Sulfatase (rhHNS) in Cerebrospinal Fluid (CSF)

Time: Pre-dose, 4, 48 hours on Week 0 and Week 48

Description: Cmax of rhHNS in serum was evaluated using enzyme-linked immunosorbent assay (ELISA) method and liquid chromatography tandem mass spectrometry (LC-MS) method.

Measure: Maximum Observed Drug Concentration (Cmax) of Recombinant Human Heparan-N-Sulfatase (rhHNS) in Serum

Time: Predose, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, and 48 h post-dose on Week 0 and Week 48

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 S298P

2. The presence of at least one S298P mutation in SGSH, associated with attenuated disease OR there is documentation of the S298P mutation in a sibling affected by MPS IIIA, provided parental consent is obtained to use this information. --- S298P ---

2. The presence of at least one S298P mutation in SGSH, associated with attenuated disease OR there is documentation of the S298P mutation in a sibling affected by MPS IIIA, provided parental consent is obtained to use this information. --- S298P --- --- S298P ---



HPO Nodes