Clinical trial NCT03508947: Safety and Tolerability of WVE-210201 in Patients With Duchenne Muscular Dystrophy
Official title: A Multicenter, Double-blind, Placebo-controlled, Phase 1 Study of WVE-210201 Administered Intravenously to Patients With Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: Wave Life Sciences Ltd.
Sponsor class: INDUSTRY
First posted: 2018-04-26
Enrollment: 36
Sex: MALE
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Safety: Number of patients with adverse events (AEs)
timeFrame: Day 1 to Day 85 (end of study)
measure: Safety: Severity of AEs
timeFrame: Day 1 to Day 85 (end of study)
measure: Safety: Number of patients with serious AEs (SAEs)
timeFrame: Day 1 to Day 85 (end of study)
measure: Safety and Tolerability: Number of patients who withdraw due to AEs
timeFrame: Day 1 to Day 85 (end of study)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum observed concentration (Cmax)
timeFrame: Day 1, Day 2, and Day 8
measure: PK: Time of occurrence of Cmax (tmax)
timeFrame: Day 1, Day 2, and Day 8
measure: PK: Area under the plasma concentration-time curve (AUC 0-t)
timeFrame: Day 1, Day 2, and Day 8
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Rare Disease Research, LLC.
state: Georgia
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: London
country: Canada
facility: London Health Sciences Centre - Hospital
state: Ontario
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Messina
country: Italy
facility: U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
city: Milano
country: Italy
facility: U.O. Immunologia Pediatrica
city: Nijmegen
country: Netherlands
facility: Radbound University Nijmegen Medical Care
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
city: London
country: United Kingdom
facility: UCL Institute of Child Health & Great Ormond Street Hospital for Children
Study officials:
affiliation: Wave Life Sciences Ltd.
name: Michael A Panzara, MD, MPH
role: STUDY_DIRECTOR
References: