Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (FORWARD-53)

NCT04906460 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: WVE-N531-001
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 5

Brief Summary

This is a Phase 1b/2 open-label study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effects of intravenous (IV) WVE-N531 in patients with Duchenne muscular dystrophy (DMD). To participate in the study, patients must have a documented mutation of the DMD gene that is amenable to exon 53 skipping intervention. This study has 3 parts, Part A, Part B, including Part B Extension Arm, and Part C. Part A is completed. Part B is completed. Following completion of Part B, all patients elected to continue to receive study drug in the optional Part B open-label Extension Arm. Part C has been added to the study and will enroll new patients.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (3)

• Part A: Safety: Proportion of patients with adverse events (AEs)

  Day 1 (initial dose) up to 24 weeks after the last dose of Part A

• Part B: Pharmacodynamics: Dystrophin level (% normal dystrophin) as assessed by Western blot of muscle tissue following multiple doses of WVE-N531

  At Week 26 and at Week 50 of Part B

• Part C: Pharmacodynamics: Change from baseline dystrophin level (% normal dystrophin) as assessed by a validated assay analysis in muscle tissue following multiple doses of WVE-N531

  At Baseline and following 24 weeks of treatment in Part C

Secondary Outcomes (8)

• Part A: Pharmacokinetics: Concentration of WVE-N531 in muscle tissue

  Day 1 (initial dose) through 2 weeks after the last dose of Part A

• Part A: Pharmacodynamics: Dystrophin level (% normal dystrophin) as assessed by Western blot of muscle tissue following multiple doses of WVE-N531

  Day 1 (initial dose) through 2 weeks after the last dose of Part A

• Part B: North Star Ambulatory Assessment (NSAA) (Version 2.0), including time to stand and a timed 10-meter walk/run, with a range of 0 to 34 where higher scores indicate better outcome.

  Collected at baseline, Weeks 24 and 48 of Part B, at baseline and Weeks 26 and 50 of the Extension Arm

• Part B: Performance of the Upper Limb (PUL) (Version 2.0) with a range of 0 to 64 where higher scores indicate a better outcome.

  Collected at baseline, Weeks 24 and 48 of Part B, at baseline and Weeks 26 and 50 of the Extension Arm

• Part B: Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)

  Collected at baseline, Weeks 24 and 48 of Part B, at baseline and Weeks 26 and 50 of the Extension Arm

Study Arms (1)

WVE-N531

EXPERIMENTAL

Drug: WVE-N531

Interventions

WVE-N531 DRUG

WVE-N531 is an antisense oligonucleotide (ASO)

WVE-N531

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Part A and Part B:
• Part A patients may be screened for Part B upon completion of a washout period of ≥18 weeks from last dose in Part A. New patients may also be screened for Part B
• Diagnosis of DMD based on clinical phenotype.
• Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
• Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) (Part B ).
• Ambulatory or non-ambulatory male
• Stable pulmonary and cardiac function, as measured by the following: (Part B):
• \. 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 (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
• Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.
• \. Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy that occurred ≥6 months prior to Screening and no changes in dose ≤3 months prior to Screening visit (Part B ).
• Part C
• New patients to be screened for Part C.
• Diagnosis of DMD based on clinical phenotype.
• Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
• Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) .

You may not qualify if:

• Clinically significant medical finding on the physical examination other than DMD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the study procedures.
• Part B and Part C: Major surgery within 3 months prior to Day 1 or planned major surgery for any time during the study.
• Part B: Diagnosis of active alcohol, cannabinoid, or other substance use disorder (except nicotine) within 6 months prior to the Screening visit
• Part C: Any recreational substance use (including prescribed cannabinoids), with the exception of nicotine, irrespective of legality, within 2 months prior to Screening and/or unwilling to refrain from such use for the duration of the study.

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (5)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3500, United States

RECRUITING

Rare Disease Research LLC

Atlanta, Georgia, 30329, United States

RECRUITING

Istiklal Hospital/ Clinical Research Unit

Amman, Jordan

RECRUITING

The Specialty Hospital (TSH)/ Advanced Clinical Center

Amman, Jordan

RECRUITING

Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust

Headington, Oxford, OX3 9DU, United Kingdom

RECRUITING

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

• Medical Director, MD

  Wave Life Sciences

  STUDY DIRECTOR

Central Study Contacts

Clinical Operations

CONTACT

855-215-4687; clinicaltrials@wavelifesci.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: May 28, 2021
• Study Start: September 28, 2021
• Primary Completion (Estimated): June 27, 2026
• Study Completion (Estimated): April 24, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (2); JO (2)