Back to resultsA Randomized, Double-blind, Placebo-controlled Study of Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy (DMD)
Primary Purpose
Muscular Dystrophy, Duchenne
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
delandistrogene moxeparvovec
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring Duchenne Muscular Dystrophy, Gene-Delivery, DMD, Ambulatory, Pediatric, North Star Ambulatory Assessment (NSAA), Percent Dystrophin Positive Fibers (PDPF)
Eligibility Criteria
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 ECHO.
- Prior or ongoing medical condition on physical examination, ECG, or laboratory findings that could adversely affect subject 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.
Sites / Locations
- David Geffen School of Medicine at UCLA
- Nationwide Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2
Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2
Arm Description
Participant will receive delandistrogene moxeparvovec at Part 1 followed by matching placebo at Part 2 followed by an open-label extension at Part 3.
Participant will receive matching placebo at Part 1 followed by delandistrogene moxeparvovec at Part 2 followed by an open-label extension at Part 3.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT03769116
First Posted
December 6, 2018
Last Updated
October 10, 2023
Sponsor
Sarepta Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03769116
Brief Title
A Randomized, Double-blind, Placebo-controlled Study of Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy (DMD)
Official Title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial for Duchenne Muscular Dystrophy Using SRP-9001
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
December 5, 2018 (Actual)
Primary Completion Date
December 8, 2020 (Actual)
Study Completion Date
August 16, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy, Duchenne
Keywords
Duchenne Muscular Dystrophy, Gene-Delivery, DMD, Ambulatory, Pediatric, North Star Ambulatory Assessment (NSAA), Percent Dystrophin Positive Fibers (PDPF)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2
Arm Type
Experimental
Arm Description
Participant will receive delandistrogene moxeparvovec at Part 1 followed by matching placebo at Part 2 followed by an open-label extension at Part 3.
Arm Title
Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2
Arm Type
Experimental
Arm Description
Participant will receive matching placebo at Part 1 followed by delandistrogene moxeparvovec at Part 2 followed by an open-label extension at Part 3.
Intervention Type
Genetic
Intervention Name(s)
delandistrogene moxeparvovec
Other Intervention Name(s)
SRP-9001, delandistrogene moxeparvovec-rokl, ELEVIDYS
Intervention Description
Single IV infusion of delandistrogene moxeparvovec
Intervention Type
Genetic
Intervention Name(s)
placebo
Intervention Description
Single IV infusion of matching placebo
Primary Outcome Measure Information:
Title
Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content
Description
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.
Time Frame
Baseline, Week 12 (Part 1)
Title
Change From Baseline at Week 48 in North Star Ambulatory Assessment (NSAA) Total Score
Description
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.
Time Frame
Baseline, Week 48 (Part 1)
Other Pre-specified Outcome Measures:
Title
Change From Baseline at Week 48 in NSAA Total Score by Age Group
Description
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.
Time Frame
Baseline, Week 48 (Part 1)
Title
Baseline NSAA Total Score by Age Group
Description
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.
Time Frame
Baseline
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Randomized, Double-blind, Placebo-controlled Study of Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy (DMD)
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