A 2-part Phase 2 Study of Safety, Pharmacokinetics and Biomarkers in Children With Duchenne Muscular Dystrophy Including a Randomized, Double-Blind, Placebo-Controlled Part A, Followed by an Open-Label Part B
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 76
- 试验地点
- 14
- 主要终点
- Number of adverse events during treatment with sevasemten or placebo
研究概览
简要总结
The LYNX study is a 2-part, multicenter, Phase 2 study of safety, pharmacokinetics and biomarkers in children with Duchenne muscular dystrophy including a randomized, double-blind, placebo-controlled part A, followed by an open-label part B.
详细描述
This 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 72 children with DMD treated with oral, once-daily sevasemten for up to 48 months. This study will have up to a 4-week Screening period, a 12-week randomized, double-blind, placebo controlled treatment period (Part A), up to a 196-week open-label extension period (Part B), and a 2-week follow up period.
Approximately 72 participants aged 4 to 9 years inclusive will be randomized to sevasemten or placebo in a 2:1 ratio. Five dose cohorts (C1, C2, C3, C4 and C5) of approximately 9 participants each will be enrolled sequentially. Approximately 18 total additional participants may be added across Cohorts 2, 3, or 4.
An additional cohort, Cohort 2NS, to include participants (aged 4 to 7 years inclusive) not currently treated with corticosteroids, will enroll approximately 9 participants after Cohort 2 safety review and in parallel with the additional 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
- 4 Years 至 9 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •A documented mutation on the DMD gene and phenotype consistent with Duchenne muscular dystrophy.
- •Able to complete the stand from supine in ≤ 10 seconds and able to perform the 4-stair climb in < 10 seconds at the Screening visit.
- •Body weight greater than or equal to 15 kg and less than 35 kg at the Screening visit.
- •For Cohorts 1, 2, 3, 4 and 5:
- •Aged 4-9 years on a stable dose of corticosteroids for a minimum of 6 months prior to the Baseline visit.
- •For Cohort 2 Non-Steroid (Cohort 2NS):
- •Aged 4-7 years not on corticosteroids within 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 testing.
- •A forced vital capacity < 60% predicted at the Screening visit for those participants who are > 8 years old at Screening.
- •A cardiac echocardiography showing left ventricular ejection < 45% at the Screening visit.
- •Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the Screening visit in the present study.
- •Receipt of a stable dose of an approved exon-skipping therapy with a treatment duration of less than 1 year prior to the Screening visit.
- •For Cohort 2 Non-Steroid (Cohort 2NS):
- •Receipt of oral corticosteroids for the treatment of Duchenne muscular dystrophy in the previous 6 months. Participants will not be tapered off steroids for the purpose of this study and oral corticosteroids for the treatment of Duchenne muscular dystrophy may be initiated after the Week 16 visit.
研究组 & 干预措施
Cohort 4
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Cohort 4
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten Dose 4 (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)
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 3
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Cohort 5
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten Dose 5 (Drug)
Cohort 5
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Cohort 2NS
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten Dose 2 (Drug)
Cohort 2NS
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: 48 months
All participants
Severity of adverse events during treatment with sevasemten or placebo
时间窗: 48 months
All participants
次要结局
- Incidence of laboratory test-related treatment emergent adverse events(48 months)
- Pharmacokinetics as measured by steady state plasma concentration(48 months)
- Change from Baseline in serum creatinine kinase(12 weeks)
- Change from Baseline in fast skeletal muscle troponin I(12 weeks)