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

An Open-label Phase 1b/2 Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: WVE-N531

Detailed Description

Following completion of Part A, eligible patients rolled over into Part B to continue to receive treatment. In addition, new patients were enrolled up to a total of 11 patients in Part B. All patients received WVE-N531 at 10 mg/kg every other week (Q2W) until competent authority approval of a protocol update, when all patients were switched to Q4W dosing. Muscle biopsies were performed following 24 weeks and for new Part B patients (those that did not take part in Part A) following 48 weeks of treatment. Following completion of Part B, all patients elected to continue to receive study drug at Q4W for up to 1 year in an optional Part B Extension Arm.

For this portion of the study, up to 15 new patients will be enrolled into Part C of the study. All patients will undergo an open muscle biopsy, at baseline and following 24 weeks of treatment.

The primary endpoint for Part B is the measurement of dystrophin protein levels. Participants will also be evaluated for safety, tolerability, digital and functional endpoints.

The primary endpoint for Part C is the measurement of dystrophin protein levels. Participants will also be evaluated for safety, tolerability, digital and functional endpoints. Safety monitoring will occur through 10 months after the last dose.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: 855-215-4687; Email: Clinicaltrials@wavelifesci.com

Study Locations

• Jordan
  • Amman, Jordan
    • Recruiting
    • Istiklal Hospital/ Clinical Research Unit
    • Contact: Muath Alqurashi, Dr; Email: drmuathalqurashi@yahoo.com
    • Principal Investigator: Muath Alqurashi, Dr
  • Amman, Jordan
    • Recruiting
    • The Specialty Hospital (TSH)/ Advanced Clinical Center
    • Contact: Mai Bader, Dr; Email: dr.mai.bader@hotmail.com
    • Principal Investigator: Mai Bader, Dr
• United Kingdom
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9DU
      • Recruiting
      • Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust
      • Contact: Laurent Servais, MD, PhD; Phone Number: 01865 227503; Email: Laurent.Servais@ouh.nhs.uk
      • Principal Investigator: Laurent Servais, MD, PhD
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202-3500
      • Recruiting
      • Arkansas Children's Hospital
      • Contact: Aravindhan Veerapandiyan, Dr; Phone Number: 501-364-1850; Email: aveerapandiyan@uams.edu
      • Principal Investigator: Aravindhan Veerapandiyan, Dr
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Rare Disease Research LLC
      • Contact: Scott Batchelor, Dr; Phone Number: 404-782-8239; Email: sbatchelor@rarediseaseresearch.com
      • Principal Investigator: Scott Batchelor, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Part A and Part B:

1. 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
2. Diagnosis of DMD based on clinical phenotype.
3. Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
4. Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) (Part B ).
5. Ambulatory or non-ambulatory male
6. Stable pulmonary and cardiac function, as measured by the following: (Part B):

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 (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.

7.Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.

8. 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

1. New patients to be screened for Part C.
2. Diagnosis of DMD based on clinical phenotype.
3. Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
4. Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) .
5. Ambulatory male
6. Stable pulmonary and cardiac function, as measured by the following:

1. Reproducible percent predicted forced vital capacity (FVC) ≥50%; 2. Left ventricular ejection fraction (LVEF) >55% in patients as measured (and documented) by echocardiogram (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.

7. Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.

8. 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 .

Exclusion Criteria:

1. 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.
2. Part B and Part C: Major surgery within 3 months prior to Day 1 or planned major surgery for any time during the study.
3. Part B: Diagnosis of active alcohol, cannabinoid, or other substance use disorder (except nicotine) within 6 months prior to the Screening visit
4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WVE-N531	Drug: WVE-N531; WVE-N531 is an antisense oligonucleotide (ASO)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Part C: 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 and Week 24 of Part C
Part C: 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 and Week 24 of Part C
Part C: Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)	Collected at baseline and Week 24 of Part C

Collaborators and Investigators

• Sponsor: Wave Life Sciences Ltd.
• Investigators: Study Director: Medical Director, MD, Wave Life Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Estimated): June 27, 2026
• Study Completion (Estimated): April 24, 2027

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Estimated): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: WVE-N531-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes