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

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)

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)

Study Overview

• Status: Terminated
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: WVE-210201 (suvodirsen); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
  • Liege
    • Liège, Liege, Belgium, 4000
      • Institut de Myologie
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B6A8
      • Alberta Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre - Hospital
• Czechia
  • Praha 5, Czechia, 15006
    • Fakultni nemocnice v Motole
• France
  • Paris, France, 75012
    • Hopital Armand Trosseau
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67098
      • Hopitaux Universitaires de Strasbourg
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Hôpital des Enfants
• Italy
  • Messina, Italy, 98125
    • U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
  • Milano, Italy, 20132
    • Ospedale San Reffaele Via Olgettina, 60
  • Roma, Italy, 8, 00168
    • Fondazione Policlinico Universitario A Gemelli
  • Lazio
    • Roma, Lazio, Italy, 165
      • Ospedale Pediatrico Bambino Gesù
• Sweden
  • Göteborg, Sweden, 41650
    • Drottning Silvias Barn Och Ungdomssjukhus
• United Kingdom
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom, WC1N EH
    • Great Ormond Street Hospital (GOSH)
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC.
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wave Life Sciences Ltd.
• Investigators: Study Director: Michael A Panzara, MD, MPH, Wave Life Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): January 9, 2020

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 5, 2019
• First Posted (Actual): April 8, 2019

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: WVE-DMDX51-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No