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

A Multicenter, Double-blind, Placebo-controlled, Phase 1 Study of WVE-210201 Administered Intravenously to Patients With Duchenne Muscular Dystrophy

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: WVE-210201; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
  • Liège, Belgium
    • Chr de La Citadelle
• Canada
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Centre - Hospital
• France
  • Paris, France
    • Hopital Armand Trousseau
• Italy
  • Messina, Italy, 98125
    • U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
  • Milano, Italy, 20132
    • U.O. Immunologia Pediatrica
• Netherlands
  • Nijmegen, Netherlands, 6525 GC
    • Radbound University Nijmegen Medical Care
• United Kingdom
  • Bristol, United Kingdom
    • University Hospitals Bristol NHS Foundation Trust
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's Hospital
  • London, United Kingdom, SE1 7EH
    • Evelina London Children's Hospital
  • London, United Kingdom
    • UCL Institute of Child Health & Great Ormond Street Hospital for Children
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: WVE-210201 (Dose A) or placebo	Drug: WVE-210201; WVE-210201 is a stereopure antisense oligonucleotide (ASO); Drug: Placebo; Sodium Chloride
EXPERIMENTAL: WVE-210201 (Dose B) or placebo	Drug: WVE-210201; WVE-210201 is a stereopure antisense oligonucleotide (ASO); Drug: Placebo; Sodium Chloride
EXPERIMENTAL: WVE-210201 (Dose C) or placebo	Drug: WVE-210201; WVE-210201 is a stereopure antisense oligonucleotide (ASO); Drug: Placebo; Sodium Chloride
EXPERIMENTAL: WVE-210201 (Dose D) or placebo	Drug: WVE-210201; WVE-210201 is a stereopure antisense oligonucleotide (ASO); Drug: Placebo; Sodium Chloride
EXPERIMENTAL: WVE-210201 (Dose E) or placebo	Drug: WVE-210201; WVE-210201 is a stereopure antisense oligonucleotide (ASO); Drug: Placebo; Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Number of patients with adverse events (AEs)	Day 1 to Day 85 (end of study)
Safety: Severity of AEs	Day 1 to Day 85 (end of study)
Safety: Number of patients with serious AEs (SAEs)	Day 1 to Day 85 (end of study)
Safety and Tolerability: Number of patients who withdraw due to AEs	Day 1 to Day 85 (end of study)

Secondary Outcome Measures

Outcome Measure	Time Frame
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
PK: Area under the plasma concentration-time curve (AUC 0-t)	Day 1, Day 2, and Day 8

Collaborators and Investigators

• Sponsor: Wave Life Sciences Ltd.
• Investigators: Study Director: Michael A Panzara, MD, MPH, Wave Life Sciences Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 24, 2018
• Primary Completion (ACTUAL): March 6, 2019
• Study Completion (ACTUAL): March 6, 2019

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (ACTUAL): April 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 5, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: WVE-DMDX51-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No