A Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 228
- 试验地点
- 76
- 主要终点
- Change From Baseline in the 4-Step Ascend Velocity at Week 96
研究概览
简要总结
The main objective of this study is to evaluate the efficacy of SRP-4045 (casimersen) and SRP-4053 (golodirsen) compared to placebo in participants with DMD with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.
详细描述
This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible participants with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 milligrams/kilograms (mg/kg) SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open-label extension period in which all participants will receive open-label active treatment for 48 weeks (up to Week 144 of study).
The study will enroll approximately 222 participants. Twice as many participants will be randomized to receive active treatment as will receive placebo (2:1 randomization).
Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests, such as the 6-minute walk test (6MWT). All participants will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96.
Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study.
Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 is double-blind and randomized; Part 2 is open-label.
入排标准
- 年龄范围
- 6 Years 至 13 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
- •Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
- •Intact right and left biceps brachii muscles or 2 alternative upper arm muscle groups
- •Mean 6MWT ≥300 meters and ≤450 meters
- •Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted
排除标准
- •Treatment with gene therapy at any time
- •Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with PRO045 (BMN 045), PRO053 (BMN 053), or PRO051 (BMN 051) within 24 weeks prior to Week 1
- •Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1
- •Major surgery within 3 months prior to Week 1
- •Presence of other clinically significant illness
- •Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
SRP-4045
Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
干预措施: SRP-4045 (Drug)
SRP-4053
Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
干预措施: SRP-4053 (Drug)
Placebo followed by SRP-4045 or SRP-4053
Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
干预措施: SRP-4045 (Drug)
Placebo followed by SRP-4045 or SRP-4053
Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
干预措施: SRP-4053 (Drug)
Placebo followed by SRP-4045 or SRP-4053
Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the 4-Step Ascend Velocity at Week 96
时间窗: Baseline, Week 96
次要结局
- Change from Baseline in the Total Distance Walked During 6MWT at Week 96(Baseline, Week 96)
- Change from Baseline in Rise from Floor Velocity at Week 96(Baseline, Week 96)
- Change From Baseline in the 4-Step Ascend Velocity at Week 144(Baseline, Week 144)
- Change From Baseline in Total Distance Walked During the 10-meter walk/run (10-MWR) Velocity(Baseline, Week 96)
- Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96(Baseline, Week 96)
- Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96(Baseline, Week 48 or Week 96)
- Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96(Baseline, Week 48 or Week 96)