Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This is a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled study with an open-label extension period to evaluate the safety and efficacy of WVE-210201 (suvodirsen) in ambulatory male pediatric patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping intervention (DYSTANCE 51)

Official Title
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A Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of WVE-210201 With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy (DYSTANCE 51)

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: WVE-210201 (suvodirsen)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase Documented mutation in the Dystrophin gene associated with DMD that is amenable to exon 51 skipping Ambulatory male, able to walk independently for at least 10 meters in 10 seconds or less at the time of Screening visit (performed as part of the NSAA) Stable pulmonary and cardiac function, as measured by: Reproducible percent predicted forced vital capacity (FVC) ≥50% Left ventricular ejection fraction (LVEF) >55% in patients <10 years of age and >45% in patients ≥10 years of age, as measured (and documented) by echocardiogram Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy occurred ≥6 months prior to Screening, and no changes in dosing ≤3 months prior to Screening visit Exclusion Criteria: Cardiac insufficiency: Severe cardiomyopathy that, in the opinion of the Investigator, prohibits participation in this study; however, cardiomyopathy that is managed by angiotensin-converting-enzyme (ACE) inhibitors or beta blockers is acceptable provided the patient meets the LVEF inclusion criterion Any other evidence of clinically significant structural or functional heart abnormality A cardiac troponin I value > 0.2 ng/mL Need for daytime mechanical or non-invasive ventilation OR anticipated need for daytime mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator. Nighttime non-invasive ventilation is permitted Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) Received prior treatment with gene therapy for DMD Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection Received any investigational drug within 3 months or 5 half-lives, whichever is longer, prior to the planned Baseline biopsy collection

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 12 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WVE-210201 (3 mg/kg)<br>Weekly IV administrations of WVE-210210 at 3 mg/kg | Drug: WVE-210201 (suvodirsen)<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>|
| Experimental: WVE-210201 (4.5 mg/kg)<br>Weekly IV administrations of WVE-210210 at 4.5 mg/kg | Drug: WVE-210201 (suvodirsen)<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>|
| Placebo Comparator: Placebo<br>Weekly IV administrations of phosphate buffered saline solution visually identical in appearance to WVE-21021 | Drug: Placebo<br>* Buffered saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Dystrophin Level (% Normal Dystrophin) | US/other regions (as applicable) | Day 1 to Week 12, Week 22, or Week 46 | 
| Change From Baseline in North Star Ambulatory Assessment (NSAA) | European Union (EU)/other regions (as applicable) | Day 1 through Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in North Star Ambulatory Assessment (NSAA) | US/other regions (as applicable) | Day 1 through Week 48 | 
| Change From Baseline in Dystrophin Level (% Normal Dystrophin) | European Union (EU)/other regions (as applicable) | Day 1 to Week 12, Week 22, or Week 46 | 
| Change From Baseline in Upper Limb Proximal Strength |  | Day 1 through Week 48 | 
| Change From Baseline in 4-stair Climb |  | Day 1 through Week 48 | 
| Change From Baseline in the 10-meter Walk/Run Test |  | Day 1 through Week 48 | 
| Change From Baseline in Forced Vital Capacity |  | Day 1 through Week 48 | 
| Change From Baseline in the 95th Percentile of Stride Velocity |  | Day 1 through Week 48 | 
| Change From Baseline in NSAA | Long-term evaluation, open label from Week 48 through Week 96 | Day 1 through Week 96 |