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

NCT03769116 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: SRP-9001-1022021-000078-27
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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).

Conditions

Muscular Dystrophy, Duchenne

Keywords

Duchenne Muscular Dystrophy; Gene-Delivery; DMD; Ambulatory; Pediatric; North Star Ambulatory Assessment (NSAA); Percent Dystrophin Positive Fibers (PDPF)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Change From Baseline at Week 48 in Time to Rise From the Floor

  Baseline, Week 48 (Part 1)

• Change From Baseline at Week 48 in Time to Ascend 4 Steps

  Baseline, Week 48 (Part 1)

• Change From Baseline at Week 48 in Time of 10-meter Timed Test

  Baseline, Week 48 (Part 1)

• Change From Baseline at Week 48 in Time of 100-meter Timed Test

  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, Week 12 (Part 1)

Other Outcomes (2)

• Baseline NSAA Total Score by Age Group

  Baseline

• Change From Baseline at Week 48 in NSAA Total Score by Age Group

  Baseline, Week 48 (Part 1)

Study Arms (2)

Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2

EXPERIMENTAL

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; Genetic: placebo

Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2

EXPERIMENTAL

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; Genetic: placebo

Interventions

delandistrogene moxeparvovec GENETIC

Single IV infusion of delandistrogene moxeparvovec

Also known as: SRP-9001, delandistrogene moxeparvovec-rokl, ELEVIDYS

Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2; Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2

placebo GENETIC

Single IV infusion of matching placebo

Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2; Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2

Eligibility Criteria

• Age: 4 Years - 7 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (2)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (1)

• Zaidman CM, Proud CM, McDonald CM, Lehman KJ, Goedeker NL, Mason S, Murphy AP, Guridi M, Wang S, Reid C, Darton E, Wandel C, Lewis S, Malhotra J, Griffin DA, Potter RA, Rodino-Klapac LR, Mendell JR. Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged >/=4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR). Ann Neurol. 2023 Nov;94(5):955-968. doi: 10.1002/ana.26755. Epub 2023 Sep 7.

  PMID: 37539981 DERIVED

Related Links

• SRP-9001-102 Plain Language Study Summary

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Caution should be taken in interpreting the treatment effect on the 6-7 years-old age group due to differences in baseline prognostic functional characteristics for certain assessments in treated versus placebo in Part 1.

Results Point of Contact

• Title: Medical Director
• Organization: Sarepta Therapeutics, Inc.

SareptAlly@sarepta.com

888-727-3782

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 7, 2018
• Study Start: December 5, 2018
• Primary Completion: December 8, 2020
• Study Completion: August 16, 2023
• Last Updated: November 14, 2024
• Results First Posted: September 15, 2023

Record last verified: 2024-11

Locations

US (2)