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

NCT03508947 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: WVE-DMDX51-001
• Study Type: interventional
• Target: 36
• Locations: 7 countries
• Sites: 13

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.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• 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

Study Arms (5)

WVE-210201 (Dose A) or placebo

EXPERIMENTAL

Drug: WVE-210201; Drug: Placebo

WVE-210201 (Dose B) or placebo

EXPERIMENTAL

Drug: WVE-210201; Drug: Placebo

WVE-210201 (Dose C) or placebo

EXPERIMENTAL

Drug: WVE-210201; Drug: Placebo

WVE-210201 (Dose D) or placebo

EXPERIMENTAL

Drug: WVE-210201; Drug: Placebo

WVE-210201 (Dose E) or placebo

EXPERIMENTAL

Drug: WVE-210201; Drug: Placebo

Interventions

WVE-210201 DRUG

WVE-210201 is a stereopure antisense oligonucleotide (ASO)

WVE-210201 (Dose A) or placebo; WVE-210201 (Dose B) or placebo; WVE-210201 (Dose C) or placebo; WVE-210201 (Dose D) or placebo; WVE-210201 (Dose E) or placebo

Placebo DRUG

Sodium Chloride

WVE-210201 (Dose A) or placebo; WVE-210201 (Dose B) or placebo; WVE-210201 (Dose C) or placebo; WVE-210201 (Dose D) or placebo; WVE-210201 (Dose E) or placebo

Eligibility Criteria

• Age: 5 Years - 18 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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 within one year prior to enrollment into the study.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (13)

Rare Disease Research, LLC.

Atlanta, Georgia, 30318, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

Location

CHR de la Citadelle

Liège, Belgium

Location

London Health Sciences Centre - Hospital

London, Ontario, Canada

Location

Hôpital Armand Trousseau

Paris, France

Location

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

Messina, 98125, Italy

Location

U.O. Immunologia Pediatrica

Milan, 20132, Italy

Location

Radbound University Nijmegen Medical Care

Nijmegen, 6525 GC, Netherlands

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, United Kingdom

Location

Alder Hey Children's Hospital

Liverpool, L12 2AP, United Kingdom

Location

Evelina London Children's Hospital

London, SE1 7EH, United Kingdom

Location

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

London, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Michael A Panzara, MD, MPH

  Wave Life Sciences Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2018
• First Posted: April 26, 2018
• Study Start: January 24, 2018
• Primary Completion: March 6, 2019
• Study Completion: March 6, 2019
• Last Updated: April 8, 2019

Record last verified: 2019-04

Locations

BE (3); US (1); FR (1); NL (1); IT (2); CA (1); GB (4)