Becker Muscular Dystrophy
Conditions
Keywords
Becker Muscular Dystrophy
Brief summary
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.
Detailed description
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. Part 2: GRAND CANYON or Cohort 6 is a double-blind, randomized, placebo-controlled design to investigate the safety and efficacy of sevasemten in adults with Becker muscular dystrophy after 18 months of treatment. Approximately 120 adults with Becker muscular dystrophy are planned to enroll in this study. This study will have up to a 4-week Screening period, an 18-month Treatment period, followed by a 4-week follow-up period. Approximately 120 adult participants will be randomized in Cohort 6 in a 2:1 ratio either to sevasemten or placebo.
Interventions
DRUGSevasemten 10 mg
Sevasemten is administered orally once per day
DRUGSevasemten 5 mg
Sevasemten is administered orally once per day
DRUGSevasemten 12.5 mg
Sevasemten is administered orally once per day
DRUGPlacebo
Placebo is administered orally once per day
Sponsors
Edgewise Therapeutics, Inc.
Medpace, Inc.
ImagingNMD
SYSNAV
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
12 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
The CANYON Study including the adolescent cohorts are fully enrolled. GRAND CANYON eligibility is listed below. Key Inclusion Criteria: 1. 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. 2. Able to complete the 100-meter timed test in \< 200 seconds with or without use of mobility aid devices. 3. Able to perform the North Star Ambulatory Assessment scale and achieve a score of 5 to 32, inclusive. Key
Exclusion criteria
1. 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. 2. Cardiac echocardiogram ejection fraction \< 40% 3. Forced vital capacity predicted \<60% or using daytime ventilatory support 4. Receipt of oral corticosteroids for the treatment of BMD in the previous 6 months. 5. Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the screening visit in the present study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events in those treated with sevasemten or placebo | 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 | 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) | All participants |
| Change from Baseline in serum Creatine Kinase | 12 Months (CANYON Cohorts 1, 2) | Adult participants |
| Change from Baseline in the North Star Ambulatory Assessment scale | 18 months (GRAND CANYON Cohort 6) | Adult participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in the protein fast skeletal muscle Troponin I | 12 months (CANYON Cohorts 1, 2), 18 months (GRAND CANYON Cohort 6) | Adult participants |
| Change from Baseline in the North Star Ambulatory Assessment scale | 12 Months (CANYON Cohorts 1, 2) | Adult participants |
| 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) | Adult participants |
| Change from Baseline in the 10-meter walk/run test | 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) | Adult participants |
| Change from Baseline in 100-meter timed test | 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) | Adult participants |
| Change from Baseline in stride velocity (95th percentile) | 18 Months (GRAND CANYON Cohort 6) | Adult participants |
| Pharmacokinetics as measured by steady state plasma concentration | 12 Months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) | All participants |
| Change from Baseline in growth as assessed by height centile on World Health Organization growth charts | 12 months (CANYON Cohorts 4, 5) | Adolescent participants |
| Month 18 change from Baseline in fat fraction of upper leg muscles as assessed by Magnetic Resonance Imaging | 18 months (GRAND CANYON Cohort 6) | Adult participants |
Countries
Australia, Belgium, Denmark, France, Germany, Israel, Italy, Netherlands, New Zealand, Spain, United Kingdom, United States
Contacts
STUDY_CHAIRJoanne Donovan, MD, PhD
Edgewise Therapeutics, Inc.
STUDY_CHAIRRoxana D. Dreghici
Edgewise Therapeutics, Inc.
Outcome results
None listed