Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy

Study Overview
=================
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

Detailed Description
-----------------
The study will include approximately 15 patients. An initial cohort will receive ascending doses of WVE-N531. Up to 4 dose levels (administered ≥4 weeks apart) will be evaluated in order to select a dose level for further multiple dose evaluation. The initial patients will receive up to 3 additional doses every other week at that dose level. Additional patients will then be enrolled and dosed every other week at that level. All patients will receive a maximum of 7 total doses followed by a minimum 8 week safety monitoring period.

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

Conditions
-----------------
Duchenne Muscular Dystrophy

Intervention / Treatment
-----------------
* Drug: WVE-N531


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase. 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). Stable pulmonary and cardiac function, as measured by the following: Reproducible percent predicted forced vital capacity (FVC) ≥50%; 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. Adequate deltoid muscle at Screening to perform open muscle biopsies. 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: Cardiac insufficiency: Severe cardiomyopathy that, in the opinion of the Investigator, prohibits participation in this study; however, cardiomyopathy that is managed by angiotensin-converting-enzyme (ACE) inhibitors or beta blockers is acceptable provided the participant meets the LVEF inclusion criterion. Any other evidence of clinically significant structural or functional heart abnormality. Need for daytime mechanical or noninvasive ventilation OR anticipated need for daytime mechanical or noninvasive ventilation within the next year in the opinion of the Investigator. Nighttime noninvasive ventilation is permitted. Received prior treatment with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) or drisapersen. Received prior treatment with gene therapy for DMD. Received treatment with ataluren, viltolarsen, eteplirsen, or golodirsen within the 14 weeks prior to Screening. Received any investigational drug within 3 months or 5 half-lives, whichever is longer prior to Screening.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WVE-N531<br> | Drug: WVE-N531<br>* WVE-N531 is an antisense oligonucleotide (ASO)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Proportion of patients with adverse events (AEs) |  | Day 1 (initial dose) to a minimum of 8 weeks after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Concentration of WVE-N531 in muscle tissue |  | Day 1 (initial dose) through 2 weeks after the last dose | 
| 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 |