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: 6 months to 3 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	Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by Western Blot. Dystrophin protein was 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 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	Measure Description	Time Frame
Change From Baseline at Week 48 in Time to Rise From the Floor	This functional assessment was performed as a part of the NSAA and measures the time taken to rise from supine to standing. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.	Baseline, Week 48 (Part 1)
Change From Baseline at Week 48 in Time to Ascend 4 Steps	This functional assessment measures the time taken to climb 4 steps. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.	Baseline, Week 48 (Part 1)
Change From Baseline at Week 48 in Time of 10-meter Timed Test	This functional assessment measures the time needed to move 10 meters. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.	Baseline, Week 48 (Part 1)
Change From Baseline at Week 48 in Time of 100-meter Timed Test	This functional assessment measures the time needed to move 100 meters. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.	Baseline, Week 48 (Part 1)
Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by Immunofluorescence (IF) Fiber Intensity	Baseline muscle biopsies were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined using IF fiber intensity. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment and reviewed by trained evaluators. An increase in IF fiber intensity (percent control) indicates increased delandistrogene moxeparvovec dystrophin expression, relative to non-dystrophic muscle (the control).	Baseline, Week 12 (Part 1)
Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by IF Percent Dystrophin Positive Fibers (PDPF)	Baseline muscle biopsies were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by IF PDPF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment. The number of muscle fibers expressing dystrophin was quantified by independent trained evaluators. An increase in IF PDPF indicates the number of muscle fibers with increased delandistrogene moxeparvovec dystrophin expression.	Baseline, Week 12 (Part 1)
Participants Experiencing Adverse Events (AEs) Since Treatment With Delandistrogene Moxeparvovec	Participants experiencing AEs are reported based upon the time to AE onset after delandistrogene moxeparvovec infusion. Each analysis set includes data from both arms and is based upon the Delandistrogene Moxeparvovec-treated Population: all participants who were treated with delandistrogene moxeparvovec in Part 1 or Part 2. 'Delandistrogene Moxeparvovec switched over to Placebo' participants received delandistrogene moxeparvovec in Part 1, followed by placebo in Part 2. AEs experienced by participants during Parts 1, 2, and 3 of the study are reported. 'Placebo switched over to Delandistrogene Moxeparvovec' participants received placebo in Part 1, followed by delandistrogene moxeparvovec in Part 2. AEs experienced by participants during Parts 2 and 3 of the study are reported. No intervention was administered during Part 3. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	Day 1 through final study visit (approximately 4.6 years)

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.

Publications and helpful links

Helpful Links

• SRP-9001-102 Plain Language Study Summary

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 (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

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: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; 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