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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- Safety as Measured by Adverse Events Frequencies (by Type and Severity)
研究概览
简要总结
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, pharmacokinetics (PK) and pharmacodynamics (PD) of SOBI003, a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).
详细描述
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. Patients between 1 and 6 years of age who have not received previous treatment for MPS IIIA with an ERT, gene- or stem cell therapy will be eligible to participate in the study. The study is planned to consist of 3 dose cohorts, each comprising 3 patients. Treatment initiations will be staggered within each cohort in order to be able to observe, interpret and treat possible adverse reactions. SOBI003 is administered as weekly i.v. infusions over a period of 24 weeks. Upon completion of the 24-week treatment period with satisfactory tolerability, the patient is offered to receive continued SOBI003 treatment by participation in an extension study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 72 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained from the patient's legally authorized representative(s)
- •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
- •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)
- •Medically stable patient who is expected to be able to comply with study procedures
排除标准
- •At least one S298P mutation in the SGSH gene
- •Contraindications for anesthetic procedures, surgical procedure (venous access port) MRI scans and/or lumbar punctures
- •History of poorly controlled seizures
- •Patients is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results
- •Significant non-MPS IIIA-related central nervous system (CNS) impairment or behavioral disturbances, which in the investigator's opinion, would confound the scientific integrity or interpretation of study assessments
- •Prior administration of stem cell or gene therapy, or ERT for MPS IIIA
- •Concurrent or prior (within 30 days of enrolment into this study) participation in a study involving invasive procedures
研究组 & 干预措施
Dose group 1
SOBI003 dose 3 mg/kg once weekly for 24 weeks
干预措施: SOBI003 (Drug)
Dose group 2
SOBI003 dose 10 mg/kg once weekly for 24 weeks
干预措施: SOBI003 (Drug)
结局指标
主要结局
Safety as Measured by Adverse Events Frequencies (by Type and Severity)
时间窗: From start of first infusion up to Week 24
Number of adverse events, by type and severity, from start of infusion up to 24 weeks
次要结局
- The Observed Serum Concentration at the End of Infusion of SOBI003(Weeks 1, 2, 3, 4, 8, 12, and 24)
- The Maximum Observed Serum Concentration of SOBI003(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Weeks 1, 4, 12, and 24)
- The Minimum Observed Serum Concentration of SOBI003(Weeks 1, 4, 12, and 24)
- Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours(0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 1, 4,12, and 24)
- The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003(Weeks 1, 2, 3, 4, 8, 12, and 24)
- The Time of the End of the Infusion of SOBI003(Weeks 1, 2, 3, 4, 8, 12, and 24)
- Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid(Baseline, weeks 12, and 24)
- The Half-life(Weeks 1, 4, 12, and 24)
- SOBI003 Concentration in Cerebrospinal Fluid(Weeks 12 and 24)
- Change From Baseline in Heparan Sulfate Levels in Serum(Weeks 2, 3, 4, 8, 12 and 24)
- Number of Patients Having Anti-drug Antibodies in Serum(Weeks 2,4,8,12 and 24)
- The Time at Which the Maximum Serum Concentration of SOBI003 is Observed(Weeks 1, 4, 12, and 24)
- Clearance(Weeks 1, 4, 12, and 24)
- Patients Having Anti-drug Antibodies in Cerebrospinal Fluid(Weeks 12 and 24)
- Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score(Week 24)
- Change From Baseline in Heparan Sulfate Levels in Urine(Weeks 2, 3, 4, 8, 12 and 24)
- Change From Baseline in Age-equivalence Score(Week 24)
- Change From Baseline in PedsQL™ Family Impact Module Total Score(Week 24)
- Change From Baseline in Neurocognitive Development Quotient(Week 24)
- Change From Baseline in Gray Matter Volume(Week 24)
- Change From Baseline in Age-equivalence Score as Assessed by VABS-II(Week 24)