Phase 2 Study of EDG-5506 in Becker Muscular Dystrophy (GRAND CANYON)

Study Overview
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Brief Summary
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A study of 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 EDG-5506 in adults with Becker. CANYON is fully enrolled; GRAND CANYON is currently enrolling.

Detailed Description
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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 EDG-5506 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 EDG-5506 or placebo in a 3:1 ratio. Approximately 9 adolescent participants will enroll in Cohort 4 and randomize in a 2:1 ratio to EDG-5506 or placebo. Cohort 5 will randomize an additional 9 participants in a 2:1 ratio to either EDG-5506 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 EDG-5506 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 EDG-5506 or placebo.

Official Title
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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

Conditions
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Becker Muscular Dystrophy

Intervention / Treatment
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* Drug: EDG-5506 10 mg
* Drug: EDG-5506 5 mg
* Drug: EDG-5506 12.5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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. Key Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult Cohort 1<br>Drug: EDG-5506 Drug: Placebo | Drug: EDG-5506 10 mg<br>* EDG-5506 is administered orally once per day<br>Drug: Placebo<br>* Placebo is administered orally once per day<br>|
| Experimental: Adult Cohort 2<br>Drug: EDG-5506 Drug: Placebo | Drug: EDG-5506 10 mg<br>* EDG-5506 is administered orally once per day<br>Drug: Placebo<br>* Placebo is administered orally once per day<br>|
| Experimental: Adult Cohort 6<br>Drug: EDG-5506 Drug: Placebo | Drug: EDG-5506 10 mg<br>* EDG-5506 is administered orally once per day<br>Drug: Placebo<br>* Placebo is administered orally once per day<br>|
| Experimental: Adolescent Cohort 4<br>Drug: EDG-5506 Drug: Placebo | Drug: EDG-5506 5 mg<br>* EDG-5506 is administered orally once per day<br>Drug: Placebo<br>* Placebo is administered orally once per day<br>|
| Experimental: Adolescent Cohort 5<br>Drug: EDG-5506 Drug: Placebo | Drug: EDG-5506 12.5 mg<br>* EDG-5506 is administered orally once per day<br>Drug: Placebo<br>* Placebo is administered orally once per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events in those treated with EDG-5506 or placebo | All participants | 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) | 
| Severity of adverse events in those treated with EDG-5506 or placebo | All participants | 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) | 
| Change from Baseline in serum Creatine Kinase | Adult participants | 12 Months (CANYON Cohorts 1, 2) | 
| Change from Baseline in the North Star Ambulatory Assessment scale | Adult participants | 18 months (GRAND CANYON Cohort 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the protein fast skeletal muscle Troponin I | Adult participants | 12 months (CANYON Cohorts 1, 2), 18 months (GRAND CANYON Cohort 6) | 
| Change from Baseline in the North Star Ambulatory Assessment scale | Adult participants | 12 Months (CANYON Cohorts 1, 2) | 
| Change from Baseline in the North Star Assessment for Limb-Girdle Type Muscular Dystrophies scale | Adult participants | 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) | 
| Change from Baseline in the 10-meter walk/run test | Adult participants | 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) | 
| Change from Baseline in 100-meter timed test | Adult participants | 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) | 
| Change from Baseline in stride velocity (95th percentile) | Adult participants | 18 Months (GRAND CANYON Cohort 6) | 
| Pharmacokinetics as measured by steady state plasma concentration | All participants | 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 | Adolescent participants | 12 months (CANYON Cohorts 4, 5) | 
| Month 18 change from Baseline in fat fraction of upper leg muscles as assessed by Magnetic Resonance Imaging | Adult participants | 18 months (GRAND CANYON Cohort 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Becker Muscular Dystrophy