Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy (DYSTANCE 51)

Wave Life Sciences

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Duchenne Muscular Dystrophy

Treatments: Drug: WVE-210201 (suvodirsen); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03907072

WVE-DMDX51-003

Details and patient eligibility

About

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)

Enrollment: 6 patients

Sex: Male

Ages: 5 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase

2. Documented mutation in the Dystrophin gene associated with DMD that is amenable to exon 51 skipping

3. 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)

4. Stable pulmonary and cardiac function, as measured by:

   1. Reproducible percent predicted forced vital capacity (FVC) ≥50%
   2. 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

5. 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

1. Cardiac insufficiency:

   1. 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
   2. Any other evidence of clinically significant structural or functional heart abnormality
   3. A cardiac troponin I value > 0.2 ng/mL

2. 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

3. Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)

4. Received prior treatment with gene therapy for DMD

5. Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection

6. Received any investigational drug within 3 months or 5 half-lives, whichever is longer, prior to the planned Baseline biopsy collection

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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6 participants in 3 patient groups, including a placebo group

WVE-210201 (3 mg/kg)

Experimental group

Description:

Weekly IV administrations of WVE-210210 at 3 mg/kg

Treatment:

Drug: WVE-210201 (suvodirsen)

WVE-210201 (4.5 mg/kg)

Experimental group

Description:

Weekly IV administrations of WVE-210210 at 4.5 mg/kg

Treatment:

Drug: WVE-210201 (suvodirsen)

Placebo

Placebo Comparator group

Description:

Weekly IV administrations of phosphate buffered saline solution visually identical in appearance to WVE-21021

Treatment:

Drug: Placebo