A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial for Duchenne Muscular Dystrophy Using SRP-9001
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 4
- 主要终点
- Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of exogenous gene transfer in DMD participants by measuring biological and clinical endpoints in three parts: two 48-week randomized, double-blinded, placebo-controlled periods (Part 1 and Part 2), and an open-label follow-up period (Part 3). Participants who are randomized to placebo in Part 1 will have the opportunity for treatment with delandistrogene moxeparvovec in Part 2.
In order to provide a uniform approach to monitoring long-term safety and efficacy in participants who received SRP-9001 in a clinical trial, the Sponsor has amended Study Completion for this study to occur at Week 130. Therefore, participants have transitioned and will complete the remainder of the Part 3 follow up visits in a long-term extension study, SRP-9001-305 (NCT05967351).
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)
入排标准
- 年龄范围
- 4 Years 至 7 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Established clinical diagnosis of DMD and documented dystrophin gene mutation of DMD phenotype.
- •Indication of symptomatic muscular dystrophy by protocol-specified criteria.
- •Ability to cooperate with motor assessment testing.
- •Stable dose equivalent of oral corticosteroids for at least 12 weeks.
- •A frameshift mutation contained between exons 18 and 58 (inclusive).
排除标准
- •Impaired cardiovascular function on echocardiogram.
- •Prior or ongoing medical condition on physical examination, electrocardiogram, or laboratory findings that could adversely affect participant safety, compromise completion of follow-up, or impair assessment of study results.
- •Exposure to another investigational drug or exon skipping medication within 6 months of screening.
- •Exposure to an investigational or commercial gene therapy product.
- •Abnormal liver or renal function by protocol-specified criteria.
- •Other inclusion/exclusion criteria apply.
结局指标
主要结局
Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content
时间窗: Baseline, Week 12 (Part 1)
Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by Western Blot. Dystrophin protein was measured and then adjusted based on the percentage of muscle content in the biopsy sample. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein.
Change From Baseline at Week 48 in NSAA Total Score
时间窗: Baseline, Week 48 (Part 1)
The NSAA is a healthcare provider administered scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. During assessment, participants are asked to perform 17 different functional activities that are graded as: 2 - "Normal" - no obvious modification of activity; 1 - Modified method but achieves goal independent of assistance; 0 - Unable to achieve independently. The NSAA total score is defined as the sum of all 17 items, ranging from 0 (worst) to 34 (best). The response vector consists of the change from baseline in NSAA total score at the post-baseline visit. The model includes the covariates of treatment group, visit, treatment group by visit interaction, age group, baseline NSAA total score, and baseline NSAA total score by visit interaction. All covariates are fixed effects in this analysis. An increase in score indicates an improvement in motor function.
次要结局
- Change From Baseline at Week 48 in Time to Rise From the Floor(Baseline, Week 48 (Part 1))
- Change From Baseline at Week 48 in Time to Ascend 4 Steps(Baseline, Week 48 (Part 1))
- Change From Baseline at Week 48 in Time of 10-meter Timed Test(Baseline, Week 48 (Part 1))
- Change From Baseline at Week 48 in Time of 100-meter Timed Test(Baseline, Week 48 (Part 1))
- Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by Immunofluorescence (IF) Fiber Intensity(Baseline, Week 12 (Part 1))
- Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by IF Percent Dystrophin Positive Fibers (PDPF)(Baseline, Week 12 (Part 1))
- Participants Experiencing Adverse Events (AEs) Since Treatment With Delandistrogene Moxeparvovec(Day 1 through final study visit (approximately 4.6 years))