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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04906460
• Other study ID #: WVE-N531-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 28, 2021
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: Wave Life Sciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: May 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• WVE-N531
WVE-N531 is an antisense oligonucleotide (ASO)

Locations

Country	Name	City	State
Jordan	Istiklal Hospital/ Clinical Research Unit	Amman
Jordan	The Specialty Hospital (TSH)/ Advanced Clinical Center	Amman
United Kingdom	Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust	Headington	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Wave Life Sciences Ltd.

Countries where clinical trial is conducted

Jordan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)		Weeks 24 and 48