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

Phase 2

Terminated

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: WVE-210201 (suvodirsen); Drug: Placebo

• Registration Number: NCT03907072
• Lead Sponsor: Wave Life Sciences Ltd.

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-05
• Study First Submitted QC: 2019-04-05
• Study First Posted: 2019-04-08
• Study Start: 2019-09-04
• Primary Completion: 2019-12-16
• Study Completion: 2020-01-09
• Status Verified: 2021-04
• Results First Submitted: 2021-04-05
• Results First Submitted QC: 2021-04-29
• Last Update Submitted: 2021-04-29
• Results First Posted: 2021-05-20
• Last Update Posted: 2021-05-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 6

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
WVE-210201 (4.5 mg/kg)	WVE-210201 (suvodirsen)	Weekly IV administrations of WVE-210210 at 4.5 mg/kg
WVE-210201 (3 mg/kg)	WVE-210201 (suvodirsen)	Weekly IV administrations of WVE-210210 at 3 mg/kg
Placebo	Placebo	Weekly IV administrations of phosphate buffered saline solution visually identical in appearance to WVE-21021

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (22)

Children's Hospital of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, Bas-Rhin, France

Hôpital Des Enfants; 🇫🇷 Toulouse, Haute-Garonne, France

Yale University; 🇺🇸 New Haven, Connecticut, United States

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

Kennedy Krieger Institute; 🇺🇸 Baltimore, Maryland, United States

University of Massachusetts; 🇺🇸 Worcester, Massachusetts, United States

Universitaire Ziekenhuizen Leuven; 🇧🇪 Leuven, Belgium

Great Ormond Street Hospital (GOSH); 🇬🇧 London, United Kingdom

Fakultni Nemocnice v Motole; 🇨🇿 Praha 5, Czechia

Rare Disease Research, LLC.; 🇺🇸 Atlanta, Georgia, United States

UZ Gent; 🇧🇪 Gent, Belgium

Institut de Myologie; 🇧🇪 Liège, Liege, Belgium

Hopital Armand Trosseau; 🇫🇷 Paris, France

Ospedale Pediatrico Bambino Gesù; 🇮🇹 Roma, Lazio, Italy

U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud; 🇮🇹 Messina, Italy

Ospedale San Reffaele Via Olgettina, 60; 🇮🇹 Milano, Italy

Fondazione Policlinico Universitario A Gemelli; 🇮🇹 Roma, Italy

Drottning Silvias Barn Och Ungdomssjukhus; 🇸🇪 Göteborg, Sweden

Leeds Teaching Hospitals NHS Trust; 🇬🇧 Leeds, United Kingdom

London Health Sciences Centre - Hospital; 🇨🇦 London, Ontario, Canada

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States