A Randomized, Double-blind, Placebo-controlled Study of Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy (DMD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of exogenous gene transfer in DMD participants by measuring biological and clinical endpoints in three parts: two 48-week randomized, double-blinded, placebo-controlled periods (Part 1 and Part 2), and an open-label follow-up period (Part 3). Participants who are randomized to placebo in Part 1 will have the opportunity for treatment with delandistrogene moxeparvovec in Part 2. In order to provide a uniform approach to monitoring long-term safety and efficacy in participants who received SRP-9001 in a clinical trial, the Sponsor has amended Study Completion for this study to occur at Week 130. Therefore, participants have transitioned and will complete the remainder of the Part 3 follow up visits in a long-term extension study, SRP-9001-305 (NCT05967351).

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial for Duchenne Muscular Dystrophy Using SRP-9001

Conditions
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Muscular Dystrophy, Duchenne

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: Established clinical diagnosis of DMD and documented dystrophin gene mutation of DMD phenotype. Indication of symptomatic muscular dystrophy by protocol-specified criteria. Ability to cooperate with motor assessment testing. Stable dose equivalent of oral corticosteroids for at least 12 weeks. A frameshift mutation contained between exons 18 and 58 (inclusive). Exclusion Criteria: Impaired cardiovascular function on echocardiogram. Prior or ongoing medical condition on physical examination, electrocardiogram, or laboratory findings that could adversely affect participant safety, compromise completion of follow-up, or impair assessment of study results. Exposure to another investigational drug or exon skipping medication within 6 months of screening. Exposure to an investigational or commercial gene therapy product. Abnormal liver or renal function by protocol-specified criteria. Other inclusion/exclusion criteria 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
Interventional Model Description: Parallel up to the measurement of the primary outcome at Week 48. At the beginning of Part 2, participants who were originally assigned to placebo will have the opportunity to receive delandistrogene moxeparvovec. All participants will be followed for 5 years following treatment with delandistrogene moxeparvovec.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2<br>Participant will receive delandistrogene moxeparvovec at Part 1 followed by matching placebo at Part 2 followed by an open-label extension at Part 3. | Genetic: delandistrogene moxeparvovec<br>* Single IV infusion of delandistrogene moxeparvovec<br>* Other names: ELEVIDYS;Genetic: placebo<br>* Single IV infusion of matching placebo<br>|
| Experimental: Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2<br>Participant will receive matching placebo at Part 1 followed by delandistrogene moxeparvovec at Part 2 followed by an open-label extension at Part 3. | 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 |
| --- | --- | --- |
| Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content | Change from baseline in delandistrogene moxeparvovec dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 12. For this endpoint, 2 blocks of tissues were analyzed by Western blot, each with 2 technical replicates to determine the delandistrogene moxeparvovec dystrophin protein level as compared to a healthy individual (Percent Normal). The block average value from 2 technical replicates was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for the analysis. Dystrophin protein measured and then adjusted based on the percentage of muscle content in the biopsy sample. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein. | Baseline, Week 12 (Part 1) | 
| Change From Baseline at Week 48 in North Star Ambulatory Assessment (NSAA) Total Score | The NSAA is a healthcare provider administered scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. During assessment, participants are asked to perform 17 different functional activities that are graded as: 2 - Normal - no obvious modification of activity; 1 - Modified method but achieves goal independent of assistance; 0 - Unable to achieve independently. The NSAA total score is defined as the sum of all 17 items, ranging from 0 (worst) to 34 (best). The response vector consists of the change from baseline in NSAA total score at the post-baseline visit. The model includes the covariates of treatment group, visit, treatment group by visit interaction, age group, baseline NSAA total score, and baseline NSAA total score by visit interaction. All covariates are fixed effects in this analysis. An increase in score indicates an improvement in motor function. | Baseline, Week 48 (Part 1) | 

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