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

Phase 1

Active, not recruiting

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: WVE-N531

• Registration Number: NCT04906460
• Lead Sponsor: Wave Life Sciences Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-05-24
• Study First Submitted QC: 2021-05-24
• Study First Posted: 2021-05-28
• Study Start: 2021-09-28
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-26
• Last Update Posted: 2024-02-28
• Primary Completion: 2025-01
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 11

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
WVE-N531	WVE-N531	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (3)

The Specialty Hospital (TSH)/ Advanced Clinical Center; 🇯🇴 Amman, Jordan

Istiklal Hospital/ Clinical Research Unit; 🇯🇴 Amman, Jordan

Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust; 🇬🇧 Headington, Oxford, United Kingdom