A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD) (ENVISION)

• ClinicalTrials.gov Identifier: NCT05881408
• Recruitment Status: Recruiting
• First Posted: May 31, 2023
• Last Update Posted: March 25, 2024
• Sponsor: Sarepta Therapeutics, Inc.
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 19, 2023
• First Posted Date: May 31, 2023
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: May 31, 2023
• Estimated Primary Completion Date: January 31, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 19, 2023): Part 1: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72 [ Time Frame: Baseline, Week 72 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 28, 2023)

• Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72 [ Time Frame: Baseline, Week 72 ]
• Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72 [ Time Frame: Baseline, Week 72 ]
• Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot [ Time Frame: Week 12 ]
• Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72 [ Time Frame: Baseline, Week 72 ]
• Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) [ Time Frame: Baseline up to Week 124 ]
• Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72 [ Time Frame: Baseline, Week 72 ]
• Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72 [ Time Frame: Baseline, Week 72 ]

Original Secondary Outcome Measures (submitted: May 19, 2023)

• Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72 [ Time Frame: Baseline, Week 72 ]
• Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72 [ Time Frame: Baseline, Week 72 ]
• Part 1: Quantity of SRP-9001 Protein Expression at Week 12 as Measured by Western Blot [ Time Frame: Week 12 ]
• Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72 [ Time Frame: Baseline, Week 72 ]
• Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) [ Time Frame: Baseline up to Week 124 ]
• Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72 [ Time Frame: Baseline, Week 72 ]
• Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72 [ Time Frame: Baseline, Week 72 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
• Official Title: A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of SRP- 9001 in Non-Ambulatory and Ambulatory Subjects With Duchenne Muscular Dystrophy (ENVISION)
• Brief Summary: The study will evaluate the safety and efficacy of delandistrogene moxeparvovec gene transfer therapy in non-ambulatory and ambulatory males with DMD. This is a randomized, double-blind, placebo-controlled 2-part study. Participants will be in the study for approximately 128 weeks. All participants will have the opportunity to receive intravenous (IV) delandistrogene moxeparvovec in either Part 1 or Part 2.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

• 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

Study Arms

• Experimental: Delandistrogene Moxeparvovec followed by Placebo
  Participants will receive single IV infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at approximately 72 weeks.
  Interventions:

  • Genetic: delandistrogene moxeparvovec
  • Genetic: placebo
• Placebo Comparator: Placebo followed by Delandistrogene Moxeparvovec
  Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at approximately 72 weeks.
  Interventions:

  • Genetic: delandistrogene moxeparvovec
  • Genetic: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 19, 2023): 148
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2027
• Estimated Primary Completion Date: January 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• Cohort 1 only: Non-ambulatory per protocol specified criteria.
• Cohort 2 only: Ambulatory per protocol specified criteria and ≥8 to <18 years of age at the time of Screening.
• Ability to cooperate with motor assessment testing.
• Stable daily dose of oral corticosteroids for at least 12 weeks prior to Screening, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
• Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) antibody titers are not elevated as per protocol-specified requirements.
• A pathogenic frameshift mutation or premature stop codon contained between exons 18 and 79 (inclusive).

Exclusion Criteria:

• Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol specified time limits.
• Abnormality in protocol-specified diagnostic evaluations or laboratory tests.
• Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer.

Other inclusion or exclusion criteria could apply.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Sarepta Therapeutics Inc., For Clinical Trial Information, Select Option 4; 1-888-SAREPTA (1-888-727-3782); SareptAlly@sarepta.com

• Listed Location Countries: Italy, Japan, Spain, United States

Administrative Information

• NCT Number: NCT05881408
• Other Study ID Numbers: SRP-9001-303; 2020-002372-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sarepta Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Sarepta Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Hoffmann-La Roche

Investigators

• Study Director: Medical Director; Sarepta Therapeutics, Inc.

• PRS Account: Sarepta Therapeutics, Inc.
• Verification Date: March 2024