Clinical trial NCT03769116: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Muscular Dystrophy, Duchenne
Keywords: Duchenne Muscular Dystrophy
Gene-Delivery
DMD
Ambulatory
Pediatric
North Star Ambulatory Assessment (NSAA)
Percent Dystrophin Positive Fibers (PDPF)
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-12-07
Enrollment: 41
Sex: MALE
Minimum age (years): 4
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content
timeFrame: Baseline, Week 12 (Part 1)
measure: Change From Baseline at Week 48 in NSAA Total Score
timeFrame: Baseline, Week 48 (Part 1)
Secondary outcomes:
measure: Change From Baseline at Week 48 in Time to Rise From the Floor
timeFrame: Baseline, Week 48 (Part 1)
measure: Change From Baseline at Week 48 in Time to Ascend 4 Steps
timeFrame: Baseline, Week 48 (Part 1)
measure: Change From Baseline at Week 48 in Time of 10-meter Timed Test
timeFrame: Baseline, Week 48 (Part 1)
measure: Change From Baseline at Week 48 in Time of 100-meter Timed Test
timeFrame: Baseline, Week 48 (Part 1)
measure: Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by Immunofluorescence (IF) Fiber Intensity
timeFrame: Baseline, Week 12 (Part 1)
measure: Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by IF Percent Dystrophin Positive Fibers (PDPF)
timeFrame: Baseline, Week 12 (Part 1)
measure: Participants Experiencing Adverse Events (AEs) Since Treatment With Delandistrogene Moxeparvovec
timeFrame: Day 1 through final study visit (approximately 4.6 years)
Other outcomes:
measure: Baseline NSAA Total Score by Age Group
timeFrame: Baseline
measure: Change From Baseline at Week 48 in NSAA Total Score by Age Group
timeFrame: Baseline, Week 48 (Part 1)
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: