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

study id #: NCT03907072

condition: Duchenne Muscular Dystrophy

status: terminated

purpose:

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)

intervention: WVE-210201 (Suvodirsen), Placebo

mechanism of action: Exon-skipping to promote dystrophin production

results: https://clinicaltrials.gov/ct2/show/results/NCT03907072

last updated: January 31, 2020

start date: September 4, 2019

estimated completion: December 16, 2019

phase of development: Phase 2/Phase 3

size / enrollment: 6

primary outcomes:

• Change from baseline in dystrophin level (% normal dystrophin) [ Time Frame: Day 1 to Week 12, Week 22, or Week 46 ]
  US/other regions (as applicable)
  
• Change from baseline in North Star Ambulatory Assessment (NSAA) [ Time Frame: Day 1 through Week 48 ]
  European Union (EU)/other regions (as applicable)

secondary outcomes:

• Change from baseline in North Star Ambulatory Assessment (NSAA) [ Time Frame: Day 1 through Week 48 ]
  US/other regions (as applicable)
  
• Change from baseline in dystrophin level (% normal dystrophin) [ Time Frame: Day 1 to Week 12, Week 22, or Week 46 ]
  EU/other regions (as applicable)
  
• Change from baseline in upper limb proximal strength [ Time Frame: Day 1 through Week 48 ]
  
• Change from baseline in 4-stair climb [ Time Frame: Day 1 through Week 48 ]
  
• Change from baseline in the 10-meter walk/run test [ Time Frame: Day 1 through Week 48 ]
  
• Change from baseline in forced vital capacity [ Time Frame: Day 1 through Week 48 ]
  
• Change from baseline in the 95th percentile of stride velocity [ Time Frame: Day 1 through Week 48 ]
  
• Change from baseline in NSAA [ Time Frame: Day 1 through Week 96 ]
  Long-term evaluation, open label from Week 48 through Week 96

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

sponsor: Wave Life Sciences Ltd.

investigators: Michael A Panzara, MD, MPH

• United States, Connecticut
  Yale University
  
  
• United States, Georgia
  Rare Disease Research, LLC
  
  
• United States, Kansas
  University of Kansas Medical Center
  
  
• United States, Maryland
  Kennedy Krieger Institute
  
  
• United States, Massachusetts
  University of Massachusetts
  
  
• United States, Wisconsin
  Children’s Hospital of Wisconsin
  
  
• Belgium
  Institut de Myologie
  
  
• Belgium
  Universitair Ziekenhuis Gent
  
  
• Belgium
  Universitaire Ziekenhuizen Leuven
  
  
• Canada, Alberta
  Alberta Children’s Hospital
  
  
• Canada, Ontario
  London Health Sciences Centre
  
  
• Czechia
  Fakultni Nemocnice v Motole – Praha 5
  
  
• France
  Hopital Armand Trousseau
  
  
• France
  Hôpital des enfants
  
  
• France
  Hôpitaux Universitaires de Strasbourg
  
  
• Italy
  Fondazione Policlinico Universitario A Gemelli
  
  
• Italy
  Ospedale Pediatrico Bambino Gesù
  
  
• Italy
  Ospedale San Reffaele
  
  
• Italy
  U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
  
  
• Sweden
  Drottning Silvias Barn Och Ungdomssjukhus
  
  
• United Kingdom
  Great Ormond Street Hospital (GOSH)
  
  
• United Kingdom
  The Leeds Teaching Hospitals NHS Trust