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

Muscular Dystrophy, Duchenne Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03769116
• Other study ID #: SRP-9001-102
• Secondary ID: 2021-000078-27
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 5, 2018
• Est. completion date: August 16, 2023

Study information

• Verified date: October 2023
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: August 16, 2023
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 7 Years

Eligibility

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.

Related Conditions & MeSH terms

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Genetic:
• delandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec
• placebo
Single IV infusion of matching placebo

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	David Geffen School of Medicine at UCLA	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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
Primary	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)
Primary	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)