Duchenne Muscular DystrophyPhase 1/2NCT04906460
Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (FORWARD-53)
A Phase 1/2 study testing WVE-N531 in people with Duchenne Muscular Dystrophy, run by Wave Life Sciences USA, Inc. at 6 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 4 to 18 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- WVE-N531
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 28 Sep 2021to 24 Apr 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
- 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) .
- Ambulatory male
- 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 .
Who cannot join
- 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.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Jordan3 sites
Istiklal Hospital/ Clinical Research Unit
Amman
The Specialty Hospital (TSH)/ Advanced Clinical Center
Amman
King Abdullah University Hospital (KAUH)
Irbid
United States2 sites
Rare Disease Research LLC
Atlanta, Georgia, 30329
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3500
United Kingdom1 site
Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust
Headington, Oxford, OX3 9DU
About this study
Official title: 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.
Read the 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.
In part C of the study, 13 new patients have been enrolled . 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.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- WVE-N531
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WVE-N531Drug
WVE-N531 is an antisense oligonucleotide (ASO)
| Study group | Role | What they receive |
|---|---|---|
| WVE-N531 | Experimental | Not described Receives: Drug: WVE-N531 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Safety: Proportion of patients with adverse events (AEs)
Measured: 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
Measured: 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
Measured: At Baseline and following 24 weeks of treatment in Part C
Secondary outcomes (8)
Part A: Pharmacokinetics: Concentration of WVE-N531 in muscle tissue
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: Collected at baseline and Week 24 of Part C
Part C: Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)
Measured: Collected at baseline and Week 24 of Part C
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study start28 Sep 2021
- Primary completionOct 2026 (estimated)
- Study completion24 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wave Life Sciences USA, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, Wave Life Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04906460
- Sponsor's protocol ID
- WVE-N531-001
- Status last verified
- Oct 2026
- First submitted
- 24 May 2021
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No