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

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

This is a Phase 1b/2a 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 2 parts, Part A and Part B. Part A is complete.

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: WVE-N531

Detailed Description

In Part B, the study will include up to 12 patients. All patients will receive WVE-N531 at 10 mg/kg every other week for 48 weeks. Muscle biopsies will be performed following 24 and 48 weeks of treatment. The primary endpoint is dystrophin protein levels and participants will also be evaluated for safety, tolerability, digital and functional endpoints. Safety monitoring will occur through 18 weeks after the last dose.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan
    • Istiklal Hospital/ Clinical Research Unit
  • Amman, Jordan
    • The Specialty Hospital (TSH)/ Advanced Clinical Center
• United Kingdom
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9DU
      • Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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).
5. Ambulatory or non-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 <10 years of age and >45% in patients ≥10 years of age, as measured (and documented) by echocardiogram (ECHO) 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.
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. Major surgery within 3 months prior to Day 1 or planned major surgery for any time during the study.
3. Diagnosis of active alcohol, cannabinoid, or other substance use disorder (except nicotine) within 6 months prior to the Screening visit.

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
Pharmacodynamics: Dystrophin level (% normal dystrophin) as assessed by Western blot of muscle tissue following multiple doses of WVE-N531	Week 26 and at Week 50

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	Weeks 24 and 48
Performance of the Upper Limb (PUL) (Version 2.0) with a range of 0 to 64 where higher scores indicate a better outcome.	Weeks 24 and 48
Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)	Weeks 24 and 48

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): January 1, 2025
• Study Completion (Estimated): May 1, 2025

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 (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

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-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