A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of EDG-5506 on Safety, Biomarkers, Pharmacokinetics, and Functional Measures in Adults and Adolescents With Becker Muscular Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 244
- 试验地点
- 86
- 主要终点
- Change from Baseline in serum Creatine Kinase
研究概览
简要总结
A study of sevasemten (EDG-5506) in Becker muscular dystrophy (known as CANYON) and pivotal cohort (known as GRAND CANYON). The EDG-5506-201 CANYON study was expanded to include an additional 120 adult participants in a cohort called GRAND CANYON, that is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of sevasemten in adults with Becker.
CANYON and GRAND CANYON are fully enrolled.
详细描述
The EDG-5506-201 protocol was amended to include an additional cohort thus consists of two parts.
Part 1: CANYON is a double-blind, randomized, placebo-controlled design to investigate the effect of sevasemten on the safety, pharmacokinetics, biomarkers, and functional measures. Approximately 32 adults and 18 adolescents with Becker muscular dystrophy are planned to enroll in this study. This study will have up to a 4-week Screening period, a 12-month Treatment period, followed by a 4-week follow-up period.
Approximately 32 adult participants will randomize to Cohort 1 or Cohort 2 in a 1:1 ratio then each cohort will further randomize to sevasemten or placebo in a 3:1 ratio.
Approximately 9 adolescent participants will enroll in Cohort 4 and randomize in a 2:1 ratio to sevasemten or placebo. Cohort 5 will randomize an additional 9 participants in a 2:1 ratio to either sevasemten or placebo after Cohort 4.
CANYON is now fully enrolled.
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
- 12 Years 至 50 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •The CANYON Study including the adolescent cohorts are fully enrolled.
- •GRAND CANYON eligibility is listed below.
- •Key Inclusion Criteria:
- •Adults (aged 18 to 50 years, inclusive) with a documented dystrophin mutation and phenotype consistent with Becker muscular dystrophy, and history of being ambulatory beyond 16 years of age without steroids; history of being ambulatory beyond 18 years of age with steroids.
- •Able to complete the 100-meter timed test in < 200 seconds with or without use of mobility aid devices.
- •Able to perform the North Star Ambulatory Assessment scale and achieve a score of 5 to 32, inclusive.
排除标准
- •Medical history or clinically significant physical examination/laboratory result that, in the opinion of the investigator, would render the participant unsuitable for the study. This includes contraindications to magnetic resonance imaging such as non-compatible implanted medical devices or severe claustrophobia.
- •Cardiac echocardiogram ejection fraction < 40%
- •Forced vital capacity predicted <60% or using daytime ventilatory support
- •Receipt of oral corticosteroids for the treatment of BMD in the previous 6 months.
- •Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the screening visit in the present study.
研究组 & 干预措施
Adolescent Cohort 4
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten 5 mg (Drug)
Adult Cohort 1
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Adult Cohort 2
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten 10 mg (Drug)
Adult Cohort 2
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Adult Cohort 1
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten 10 mg (Drug)
Adult Cohort 6
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten 10 mg (Drug)
Adult Cohort 6
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Adolescent Cohort 5
Drug: Sevasemten Drug: Placebo
干预措施: Sevasemten 12.5 mg (Drug)
Adolescent Cohort 4
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
Adolescent Cohort 5
Drug: Sevasemten Drug: Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline in serum Creatine Kinase
时间窗: 12 Months (CANYON Cohorts 1, 2)
Adult participants
Number of adverse events in those treated with sevasemten or placebo
时间窗: 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6)
All participants
Severity of adverse events in those treated with sevasemten or placebo
时间窗: 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6)
All participants
Change from Baseline in the North Star Ambulatory Assessment scale
时间窗: 18 months (GRAND CANYON Cohort 6)
Adult participants
次要结局
- Change from Baseline in the protein fast skeletal muscle Troponin I(12 months (CANYON Cohorts 1, 2), 18 months (GRAND CANYON Cohort 6))
- Change from Baseline in the North Star Ambulatory Assessment scale(12 Months (CANYON Cohorts 1, 2))
- Change from Baseline in the North Star Assessment for Limb-Girdle Type Muscular Dystrophies scale(12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6))
- Change from Baseline in the 10-meter walk/run test(12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6))
- Change from Baseline in 100-meter timed test(12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6))
- Change from Baseline in stride velocity (95th percentile)(18 Months (GRAND CANYON Cohort 6))
- Pharmacokinetics as measured by steady state plasma concentration(12 Months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6))
- Change from Baseline in growth as assessed by height centile on World Health Organization growth charts(12 months (CANYON Cohorts 4, 5))
- Month 18 change from Baseline in fat fraction of upper leg muscles as assessed by Magnetic Resonance Imaging(18 months (GRAND CANYON Cohort 6))