A Randomised, Double-blind, Placebo-controlled, Efficacy and Safety Study of Suvodirsen (WVE-210201) With Open Label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy
DYSTANCE 51 is a phase 2/3 clinical trial designed to evaluate the efficacy and safety of WVE-210201 (suvodirsen) in ambulant boys with DMD mutations amenable to exon 51 skipping.
DYSTANCE 51 is comprised of two phases, a placebo-controlled phase and an open-label phase. In the placebo-controlled phase, patients will be randomized to receive suvodirsen 3 mg/kg, suvodirsen 4.5 mg/kg or placebo for 48 weeks. Dystrophin protein levels and functional outcomes will be assessed for each patient throughout the initial 48-week treatment period.
Each participant will have two biopsies in total, one at baseline, and one at either week 12, 22, or 46.
Following completion of the placebo-controlled phase of the study, patients will enter the open-label phase to receive ongoing treatment with suvodirsen. There will be no placebo or biopsies in the open label phase. However, functional assessments will continue.
Study Number: NCT03907072
Description by Wave Life Sciences Ltd
DYSTANCE 51 is a global, phase 2/3, multicentre, randomised, double-blind, placebo-controlled clinical trial that will evaluate the efficacy and safety of suvodirsen in ambulatory male paediatric patients with DMD amenable to exon 51 skipping intervention.
Primary Outcome Measures
- Change from baseline in dystrophin level (% normal dystrophin) - US/other regions (as applicable)
- Change from baseline in North Star Ambulatory Assessment (NSAA) - EU/other regions (as applicable)
Secondary Outcome Measures
- Change from baseline in North Star Ambulatory Assessment (NSAA)
- Change from baseline in dystrophin level (% normal dystrophin)
- Change from baseline in upper limb proximal strength
- Change from baseline in 4-stair climb
- Change from baseline in the 10-meter walk/run test
- Change from baseline in forced vital capacity
- Change from baseline in the 95th percentile of stride velocity
Can I take part?
- 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)
- 5 to 12 years of age (up to 13th birthday) at the time of randomisation
- 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
- 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