Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy

NCT03907072 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: WVE-DMDX51-003
• Study Type: interventional
• Target: 6
• Locations: 8 countries
• Sites: 22

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)

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Dystrophin Level (% Normal Dystrophin)

  US/other regions (as applicable)

  Day 1 to Week 12, Week 22, or Week 46

• Change From Baseline in North Star Ambulatory Assessment (NSAA)

  European Union (EU)/other regions (as applicable)

  Day 1 through Week 48

Secondary Outcomes (8)

• Change From Baseline in North Star Ambulatory Assessment (NSAA)

  Day 1 through Week 48

• Change From Baseline in Dystrophin Level (% Normal Dystrophin)

  Day 1 to Week 12, Week 22, or Week 46

• Change From Baseline in Upper Limb Proximal Strength

  Day 1 through Week 48

• Change From Baseline in 4-stair Climb

  Day 1 through Week 48

• Change From Baseline in the 10-meter Walk/Run Test

  Day 1 through Week 48

Study Arms (3)

WVE-210201 (3 mg/kg)

EXPERIMENTAL

Weekly IV administrations of WVE-210210 at 3 mg/kg

Drug: WVE-210201 (suvodirsen)

WVE-210201 (4.5 mg/kg)

EXPERIMENTAL

Weekly IV administrations of WVE-210210 at 4.5 mg/kg

Drug: WVE-210201 (suvodirsen)

Placebo

PLACEBO COMPARATOR

Weekly IV administrations of phosphate buffered saline solution visually identical in appearance to WVE-21021

Drug: Placebo

Interventions

WVE-210201 (suvodirsen) DRUG

WVE-210201 is a stereopure antisense oligonucleotide (ASO)

WVE-210201 (3 mg/kg); WVE-210201 (4.5 mg/kg)

Placebo DRUG

Buffered saline solution

Placebo

Eligibility Criteria

• Age: 5 Years - 12 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of 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 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)
• 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
• 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

You may not qualify if:

• Cardiac insufficiency:
• Any other evidence of clinically significant structural or functional heart abnormality
• A cardiac troponin I value \> 0.2 ng/mL
• 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
• Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
• Received prior treatment with gene therapy for DMD
• Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection
• Received any investigational drug within 3 months or 5 half-lives, whichever is longer, prior to the planned Baseline biopsy collection

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (22)

Yale University

New Haven, Connecticut, 06510, United States

Location

Rare Disease Research, LLC.

Atlanta, Georgia, 30318, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01605, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Institut de Myologie

Liège, Liege, 4000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

Location

Alberta Children's Hospital

Calgary, Alberta, T3B6A8, Canada

Location

London Health Sciences Centre - Hospital

London, Ontario, N6A 5W9, Canada

Location

Fakultni Nemocnice v Motole

Prague, 15006, Czechia

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, Bas-Rhin, 67098, France

Location

Hôpital Des Enfants

Toulouse, Haute-Garonne, 31059, France

Location

Hopital Armand Trosseau

Paris, 75012, France

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 165, Italy

Location

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

Messina, 98125, Italy

Location

Ospedale San Reffaele Via Olgettina, 60

Milan, 20132, Italy

Location

Fondazione Policlinico Universitario A Gemelli

Roma, 8, 00168, Italy

Location

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, 41650, Sweden

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Great Ormond Street Hospital (GOSH)

London, WC1N EH, 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

Results Point of Contact

• Title: Medical Director
• Organization: WAVE Life Sciences

clinicaltrials@wavelifesci.com

855-215-4687

Study Officials

• Michael A Panzara, MD, MPH

  Wave Life Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 8, 2019
• Study Start: September 4, 2019
• Primary Completion: December 16, 2019
• Study Completion: January 9, 2020
• Last Updated: May 20, 2021
• Results First Posted: May 20, 2021

Record last verified: 2021-04

Locations

SE (1); BE (3); FR (3); CZ (1); IT (4); GB (2); US (6); CA (2)