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Safety and Tolerability of WVE-210201 in Patients With Duchenne Muscular Dystrophy

Phase 1
Completed
Conditions
Duchenne Muscular Dystrophy
Interventions
Drug: WVE-210201
Drug: Placebo
Registration Number
NCT03508947
Lead Sponsor
Wave Life Sciences Ltd.
Brief Summary

This is a Phase 1, double-blind, placebo-controlled, single ascending dose cohort study to evaluate the safety, tolerability, and plasma concentrations of WVE-210201 in ambulatory and non-ambulatory male pediatric patients with DMD amenable to exon 51 skipping intervention.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
36
Inclusion Criteria
  • Diagnosis of Duchenne muscular dystrophy (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 or non-ambulatory male patients aged ≥5 - ≤18 years

  • 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 within one year prior to enrollment into the study.
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Exclusion Criteria
  • Severe cardiomyopathy; cardiomyopathy that is managed by angiotensin-converting enzyme (ACE) inhibitors or beta blockers is acceptable provided the patient meets the LVEF inclusion criteria.
  • Need for mechanical or non-invasive ventilation OR anticipated need for mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator.
  • Changes in nutritional or herbal supplements or concomitant medications within 1 month prior to Screening visit or plans to modify dose or regimen during the study.
  • Currently on anticoagulants or antithrombotics.
  • Received treatment with eteplirsen or ataluren within the past 14 weeks.
  • Received prior treatment with drisapersen.
  • Received any investigational drug within the past 3 months or 5 half-lives, whichever is longer.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
WVE-210201 (Dose B) or placeboPlacebo-
WVE-210201 (Dose B) or placeboWVE-210201-
WVE-210201 (Dose C) or placeboWVE-210201-
WVE-210201 (Dose C) or placeboPlacebo-
WVE-210201 (Dose A) or placeboPlacebo-
WVE-210201 (Dose A) or placeboWVE-210201-
WVE-210201 (Dose D) or placeboWVE-210201-
WVE-210201 (Dose D) or placeboPlacebo-
WVE-210201 (Dose E) or placeboWVE-210201-
WVE-210201 (Dose E) or placeboPlacebo-
Primary Outcome Measures
NameTimeMethod
Safety: Severity of AEsDay 1 to Day 85 (end of study)
Safety: Number of patients with serious AEs (SAEs)Day 1 to Day 85 (end of study)
Safety: Number of patients with adverse events (AEs)Day 1 to Day 85 (end of study)
Safety and Tolerability: Number of patients who withdraw due to AEsDay 1 to Day 85 (end of study)
Secondary Outcome Measures
NameTimeMethod
PK: Area under the plasma concentration-time curve (AUC 0-t)Day 1, Day 2, and Day 8
Pharmacokinetics (PK): Maximum observed concentration (Cmax)Day 1, Day 2, and Day 8
PK: Time of occurrence of Cmax (tmax)Day 1, Day 2, and Day 8

Trial Locations

Locations (13)

Universitaire Ziekenhuizen Leuven

🇧🇪

Leuven, Belgium

CHR de la Citadelle

🇧🇪

Liège, Belgium

Rare Disease Research, LLC.

🇺🇸

Atlanta, Georgia, United States

UZ Gent

🇧🇪

Gent, Belgium

Radbound University Nijmegen Medical Care

🇳🇱

Nijmegen, Netherlands

U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud

🇮🇹

Messina, Italy

University Hospitals Bristol NHS Foundation Trust

🇬🇧

Bristol, United Kingdom

Evelina London Children's Hospital

🇬🇧

London, United Kingdom

UCL Institute of Child Health & Great Ormond Street Hospital for Children

🇬🇧

London, United Kingdom

Hôpital Armand Trousseau

🇫🇷

Paris, France

London Health Sciences Centre - Hospital

🇨🇦

London, Ontario, Canada

U.O. Immunologia Pediatrica

🇮🇹

Milano, Italy

Alder Hey Children's Hospital

🇬🇧

Liverpool, United Kingdom

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