An Open, Single-arm, Multicenter Extension Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment 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
- 3
- 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 aim of the present study is to assess the safety, tolerability and efficacy of long-term SOBI003 treatment. SOBI003 is a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).
详细描述
This is an open, single-arm, multicenter extension study to assess the safety, tolerability and efficacy of long-term SOBI003 treatment in pediatric MPS IIIA patients. The study is an extension of the First in Human (FIH) SOBI003-001 study, allowing continuous treatment of SOBI003 for up to 2 years. Study patients who complete Week 24 of the FIH study (SOBI003-001) will be invited to continue to Week 25 in the extension study.
When entering the extension study, these patients will receive the highest dose that has been declared safe in the ongoing FIH study (SOBI003-001). Upon completion of the FIH study, an analysis aimed at selecting the dose for forthcoming studies will take place. Once the dose has been selected, this dose will be applied to all patients enrolled in the extension study. The total duration of the extension study for an individual patient is 80 weeks, resulting in a total of 104 weeks (2 years) of SOBI003 treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Months 至 78 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completion of study SOBI003-001
- •Informed consent obtained from the patient´s legally authorized representative
排除标准
- •If, in the opinion of the investigator, there are patient specific safety concerns that contraindicates further treatment with SOBI003
研究组 & 干预措施
SOBI003
SOBI003 solution, 20 mg/mL, is mixed with NaCl 0.9% infusion solution prior to administration. For a bodyweight < 25 kg, the total infusion volume is 100 mL. For a bodyweight ≥ 25 kg, the total infusion volume is 250 mL.
SOBI003 is administered as i.v. infusions given once weekly for a duration of 80 weeks (from Week 25 until Week 104 following the first 24 weeks of SOBI003 administration in the FIH study (SOBI003-001) study. The SOBI003 dose will be adjusted to the highest dose that has been declared safe by the safety review committee on the FIH study.Hence, dose adjustments may occur a couple of times on the extension study until the final decided dose has been determined.
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 infusion week 25 up to week 104
Number of adverse events, by type and severity, from week 25 up to week 104
次要结局
- Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid(Weeks 52 and 104)
- Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid(Weeks 52 and 104)
- Change From Baseline in Heparan Sulfate Levels in Serum(Weeks 38, 52, 78 and 104)
- Change From Baseline in Heparan Sulfate Levels in Urine(Weeks 38, 52, 78 and 104)
- Change From Baseline in Neurocognitive Development Quotient(Weeks 52 and 104)
- Change From Baseline in Age-equivalence Score(Week 52 and 104)
- Pediatric Quality of Life Inventory (PedsQL™) Total Score(Week 52 and 104)
- The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003(Weeks 38, 52, 78 and 104)
- The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003(Weeks 38, 52, 78 and 104)
- The Time of the End of the Infusion of SOBI003(Weeks 38, 52, 78 and 104)
- The Maximum Observed Serum Concentration of SOBI003(Weeks 38, 52, 78 and 104)
- The Time at Which the Maximum Serum Concentration of SOBI003 is Observed(Weeks 38, 52, 78 and 104)
- The Minimum Observed Serum Concentration of SOBI003(Weeks 38, 52, 78 and 104)
- Clearance(Weeks 38, 52, 78 and 104)
- Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours(0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 38, 52, 78 and 104)
- The Half-life(Weeks 38, 52, 78 and 104)
- Number of Patients Having Anti-drug Antibodies in Serum(Weeks 38, 52, 78 and 104)
- Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.(Week 52 and 104)
- Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.(Week 52 and 104)
- Age-equivalence Score as Assessed by VABS-II(Week 52 and 104)
- Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score(Week 52 and 104)
- PedsQL™ Family Impact Module Total Score(Week 52 and 104)
- Change From Baseline in PedsQL™ Family Impact Module Total Score(Week 52 and 104)
- SOBI003 Concentration in Cerebrospinal Fluid(Weeks 52 and 104)
- Change From Baseline in Age-equivalence Score as Assessed by VABS-II(Week 52 and 104)
- Change From Baseline in Gray Matter Volume(Week 52 and 104)