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

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

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).

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophy, Duchenne
• Intervention / Treatment: Genetic: delandistrogene moxeparvovec; Genetic: placebo

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2; 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; Single IV infusion of delandistrogene moxeparvovec; Other Names: SRP-9001; delandistrogene moxeparvovec-rokl; ELEVIDYS; Genetic: placebo; Single IV infusion of matching placebo
Experimental: Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2; 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; Single IV infusion of delandistrogene moxeparvovec; Other Names: SRP-9001; delandistrogene moxeparvovec-rokl; ELEVIDYS; Genetic: placebo; Single IV infusion of matching placebo

What is the study measuring?

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)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Time to Rise From the Floor	Baseline up to Week 48 (Part 1)
Change From Baseline in Time to Ascend 4 Steps	Baseline up to Week 48 (Part 1)
Change From Baseline in Time of 10 Meter Timed Test	Baseline up to Week 48 (Part 1)
Change From Baseline in Time of 100 Meter Timed Test	Baseline up to Week 48 (Part 1)
Change From Baseline in Quantity of Micro-dystrophin Expression Measured by Immunofluorescence (IF) Fiber Intensity	Baseline up to Week 12 (Part 1)
Change From Baseline in Quantity of Micro-dystrophin Expression Measured by IF Percent Dystrophin Positive Fibers (PDPF)	Baseline up to Week 12 (Part 1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 48 in NSAA Total Score by Age Group	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)
Baseline NSAA Total Score by Age Group	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). This outcome measure presents only the baseline NSAA total score of the ITT population by the following age groups: 4-5 years old; 6-7 years old.	Baseline

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Investigators: Study Director: Medical Director, Sarepta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2018
• Primary Completion (Actual): December 8, 2020
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 7, 2018

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Duchenne Muscular Dystrophy; DMD; Gene-Delivery; Ambulatory; North Star Ambulatory Assessment (NSAA); Percent Dystrophin Positive Fibers (PDPF)
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: SRP-9001-102; 2021-000078-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No