Safety and Tolerability of WVE-210201 in Patients With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This is a Phase 1, double-blind, placebo-controlled, single ascending dose cohort study to evaluate the safety, tolerability, and plasma concentrations of WVE-210201 in ambulatory and non-ambulatory male pediatric patients with DMD amenable to exon 51 skipping intervention.

Official Title
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A Multicenter, Double-blind, Placebo-controlled, Phase 1 Study of WVE-210201 Administered Intravenously to Patients With Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: WVE-210201
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Duchenne muscular dystrophy (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 or non-ambulatory male patients aged ≥5 - ≤18 years 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 within one year prior to enrollment into the study. Exclusion Criteria: Severe cardiomyopathy; cardiomyopathy that is managed by angiotensin-converting enzyme (ACE) inhibitors or beta blockers is acceptable provided the patient meets the LVEF inclusion criteria. Need for mechanical or non-invasive ventilation OR anticipated need for mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator. Changes in nutritional or herbal supplements or concomitant medications within 1 month prior to Screening visit or plans to modify dose or regimen during the study. Currently on anticoagulants or antithrombotics. Received treatment with eteplirsen or ataluren within the past 14 weeks. Received prior treatment with drisapersen. Received any investigational drug within the past 3 months or 5 half-lives, whichever is longer.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WVE-210201 (Dose A) or placebo<br> | Drug: WVE-210201<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>Drug: Placebo<br>* Sodium Chloride<br>|
| Experimental: WVE-210201 (Dose B) or placebo<br> | Drug: WVE-210201<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>Drug: Placebo<br>* Sodium Chloride<br>|
| Experimental: WVE-210201 (Dose C) or placebo<br> | Drug: WVE-210201<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>Drug: Placebo<br>* Sodium Chloride<br>|
| Experimental: WVE-210201 (Dose D) or placebo<br> | Drug: WVE-210201<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>Drug: Placebo<br>* Sodium Chloride<br>|
| Experimental: WVE-210201 (Dose E) or placebo<br> | Drug: WVE-210201<br>* WVE-210201 is a stereopure antisense oligonucleotide (ASO)<br>Drug: Placebo<br>* Sodium Chloride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of patients with adverse events (AEs) |  | Day 1 to Day 85 (end of study) | 
| Safety: Severity of AEs |  | Day 1 to Day 85 (end of study) | 
| Safety: Number of patients with serious AEs (SAEs) |  | Day 1 to Day 85 (end of study) | 
| Safety and Tolerability: Number of patients who withdraw due to AEs |  | Day 1 to Day 85 (end of study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum observed concentration (Cmax) |  | Day 1, Day 2, and Day 8 | 
| PK: Time of occurrence of Cmax (tmax) |  | Day 1, Day 2, and Day 8 | 
| PK: Area under the plasma concentration-time curve (AUC 0-t) |  | Day 1, Day 2, and Day 8 |