Clinical trial NCT03907072: Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: Wave Life Sciences Ltd.
Sponsor class: INDUSTRY
First posted: 2019-04-08
Enrollment: 6
Sex: MALE
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Dystrophin Level (% Normal Dystrophin)
timeFrame: Day 1 to Week 12, Week 22, or Week 46
measure: Change From Baseline in North Star Ambulatory Assessment (NSAA)
timeFrame: Day 1 through Week 48
Secondary outcomes:
measure: Change From Baseline in North Star Ambulatory Assessment (NSAA)
timeFrame: Day 1 through Week 48
measure: Change From Baseline in Dystrophin Level (% Normal Dystrophin)
timeFrame: Day 1 to Week 12, Week 22, or Week 46
measure: Change From Baseline in Upper Limb Proximal Strength
timeFrame: Day 1 through Week 48
measure: Change From Baseline in 4-stair Climb
timeFrame: Day 1 through Week 48
measure: Change From Baseline in the 10-meter Walk/Run Test
timeFrame: Day 1 through Week 48
measure: Change From Baseline in Forced Vital Capacity
timeFrame: Day 1 through Week 48
measure: Change From Baseline in the 95th Percentile of Stride Velocity
timeFrame: Day 1 through Week 48
measure: Change From Baseline in NSAA
timeFrame: Day 1 through Week 96
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Rare Disease Research, LLC.
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Liège
country: Belgium
facility: Institut de Myologie
state: Liege
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre - Hospital
state: Ontario
city: Praha 5
country: Czechia
facility: Fakultni Nemocnice v Motole
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
state: Bas-Rhin
city: Toulouse
country: France
facility: Hôpital Des Enfants
state: Haute-Garonne
city: Paris
country: France
facility: Hopital Armand Trosseau
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
state: Lazio
city: Messina
country: Italy
facility: U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
city: Milano
country: Italy
facility: Ospedale San Reffaele Via Olgettina, 60
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
city: Göteborg
country: Sweden
facility: Drottning Silvias Barn Och Ungdomssjukhus
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital (GOSH)
Study officials:
affiliation: Wave Life Sciences
name: Michael A Panzara, MD, MPH
role: STUDY_DIRECTOR
References: