A Phase 2 Study to Evaluate the Effect of EDG-5506 on Safety, Pharmacokinetics, and Biomarkers in Children and Adolescents With Duchenne Muscular Dystrophy Previously Treated With Gene Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 43
- 试验地点
- 7
- 主要终点
- Number of adverse events during treatment with sevasemten or placebo
研究概览
简要总结
The FOX study is a 2-part, multicenter, Phase 2 study of safety, pharmacokinetics, and biomarkers in children and adolescents with Duchenne muscular dystrophy previously treated with gene therapy including a randomized, double-blind, placebo-controlled Part A, followed by an open-label part B.
详细描述
FOX is a 2-part, multi-center, Phase 2 study to evaluate the effect of sevasemten (EDG-5506) on safety, pharmacokinetics and biomarkers of muscle damage in approximately 48 children and adolescents with Duchenne muscular dystrophy treated with oral, once-daily sevasemten. This study will have up to a 4-week Screening period, a 12-week randomized double-blind, placebo-controlled treatment period (Part A), followed by up to a 144-week open-label extension period (Part B).
Approximately forty-eight (48) participants aged 6 to 17, inclusive, will be randomized to sevasemten or placebo in a 2:1 ratio. Three dose cohorts (Cohort 1, Cohort 2 and Cohort 3) of approximately 12 participants each will be enrolled. Approximately 12 additional participants may be added to 1 of these cohorts.
After review of emerging data, the protocol was amended so all dose cohorts receive the same dose in Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Aged 6 to 17 with a documented mutation on the DMD gene and phenotype consistent with DMD.
- •Prior receipt of an AAV-based gene therapy (≥ 2 years after documented receipt of gene therapy administration or ≥ 3 years after randomization in a randomized study).
- •Able to complete stand from supine in ≤ 8 seconds at the Screening visit and able to perform the 4-stair climb in < 10 seconds at the Screening visit.
- •Body weight ≥ 15 kg at the Screening visit.
- •Treatment with a stable dose of corticosteroids for a minimum of 6 months prior to the Baseline visit.
排除标准
- •Medical history or clinically significant physical exam/laboratory result that, in the opinion of the investigator, would render the participant unsuitable for the study. This includes venous access that would be too difficult to facilitate repeated blood sampling.
- •Screening visit cardiac echocardiography showing left ventricular ejection fraction (LVEF) < 40%.
- •Receipt of an investigational drug (other than the AAV-based gene therapy per Inclusion criteria) within 30 days or 5 half-lives (whichever is longer) of the Screening visit in the present study.
- •Receipt of an exon-skipping therapy within 6 months prior to the Screening visit.
研究组 & 干预措施
Cohort 3
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Cohort 2
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten Dose 2 (Drug)
Cohort 2
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Cohort 3
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten Dose 3 (Drug)
Cohort 1
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten Dose 1 (Drug)
Cohort 1
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of adverse events during treatment with sevasemten or placebo
时间窗: 36 months
All participants
Severity of adverse events during treatment with sevasemten or placebo
时间窗: 36 months
All participants
次要结局
- Incidence of laboratory test-related treatment emergent adverse events(36 months)
- Pharmacokinetics as measured by steady state plasma concentration(36 months)
- Change from Baseline in serum creatine kinase(12 weeks)
- Change from Baseline in fast skeletal muscle troponin I(12 weeks)