A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in 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 gene transfer therapy in boys with DMD. It is a randomized, double-blind, placebo-controlled study. The participants who are randomized to the placebo arm will have an opportunity for treatment with gene transfer therapy at the beginning of the second year.

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

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: Is ambulatory and from 4 to under 8 years of age at time of randomization. Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing. 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). 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), with the exception of mutation fully contained within exon 45. 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.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 7 Years

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 intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at Year 2. | 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 Year 2. | 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 NSAA Total Score at Week 52 |  | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot, in a Subset of Participants |  | Week 12 | 
| Part 1: Change From Baseline in Time to Rise From the Floor, Time to Complete 100 and 10 Meter Walk/Run, and the Timed Stair Ascend 4 Steps Test at Week 52 |  | Baseline, Week 52 | 
| Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) Measured by a Wearable Device |  | Baseline, Week 52 | 
| Part 1: Change from Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Score in Mobility and Upper Extremity Function to Week 52 | PROMIS is a family of instruments developed and validated to assess health-related quality of life. | Baseline, Week 52 | 
| Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA |  | Baseline, Week 52 | 
| Number of Participants with a Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) |  | Baseline up to Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMD, Muscular Dystrophies, Duchenne Muscular Dystrophy, North Star Ambulatory Assessment (NSAA), Ambulatory, Pediatric, Gene-Delivery