A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)

Study Overview
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Brief Summary
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The study will evaluate the safety and efficacy of delandistrogene moxeparvovec gene transfer therapy in non-ambulatory and ambulatory males with DMD. This is a randomized, double-blind, placebo-controlled 2-part study. Participants will be in the study for approximately 128 weeks. All participants will have the opportunity to receive intravenous (IV) delandistrogene moxeparvovec in either Part 1 or Part 2.

Official Title
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A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of SRP- 9001 in Non-Ambulatory and Ambulatory Subjects With Duchenne Muscular Dystrophy (ENVISION)

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Genetic: delandistrogene moxeparvovec
* Genetic: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing. Cohort 1 only: Non-ambulatory per protocol specified criteria. Cohort 2 only: Ambulatory per protocol specified criteria and ≥8 to <18 years of age at the time of Screening. Ability to cooperate with motor assessment testing. Stable daily dose of oral corticosteroids for at least 12 weeks prior to Screening, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight). Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) antibody titers are not elevated as per protocol-specified requirements. A pathogenic frameshift mutation or premature stop codon contained between exons 18 and 79 (inclusive). Exclusion Criteria: Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol specified time limits. Abnormality in protocol-specified diagnostic evaluations or laboratory tests. Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer. Other inclusion or exclusion criteria could apply.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delandistrogene Moxeparvovec followed by Placebo<br>Participants will receive single IV infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at approximately 72 weeks. | Genetic: delandistrogene moxeparvovec<br>* Single IV infusion of delandistrogene moxeparvovec<br>* Other names: ELEVIDYS;Genetic: placebo<br>* Single IV infusion of matching placebo<br>|
| Placebo Comparator: Placebo followed by Delandistrogene Moxeparvovec<br>Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at approximately 72 weeks. | Genetic: delandistrogene moxeparvovec<br>* Single IV infusion of delandistrogene moxeparvovec<br>* Other names: ELEVIDYS;Genetic: placebo<br>* Single IV infusion of matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72 |  | Baseline, Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72 |  | Baseline, Week 72 | 
| Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72 |  | Baseline, Week 72 | 
| Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot |  | Week 12 | 
| Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72 |  | Baseline, Week 72 | 
| Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) |  | Baseline up to Week 124 | 
| Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72 |  | Baseline, Week 72 | 
| Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72 |  | Baseline, Week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ambulatory, Non-ambulatory, DMD, Gene-Delivery, Pediatric, North Star Ambulatory Assessment (NSAA), Performance of Upper Limb (PUL), Duchenne