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

• ClinicalTrials.gov Identifier: NCT05096221
• Recruitment Status: Active, not recruiting
• First Posted: October 27, 2021
• Last Update Posted: November 7, 2023
• Sponsor: Sarepta Therapeutics, Inc.
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Tracking Information

• First Submitted Date: October 14, 2021
• First Posted Date: October 27, 2021
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: October 27, 2021
• Actual Primary Completion Date: October 4, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 14, 2021): Part 1: Change From Baseline in NSAA Total Score at Week 52 [ Time Frame: Baseline, Week 52 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 3, 2023)

• Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot, in a Subset of Participants [ Time Frame: Week 12 ]
• Part 1: Change From Baseline in Time to Rise From the Floor, Time to Complete 100 and 10 Meter Walk/Run, and the Timed Stair Ascend 4 Steps Test at Week 52 [ Time Frame: Baseline, Week 52 ]
• Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) Measured by a Wearable Device [ Time Frame: Baseline, Week 52 ]
• Part 1: Change from Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Score in Mobility and Upper Extremity Function to Week 52 [ Time Frame: Baseline, Week 52 ]
  PROMIS is a family of instruments developed and validated to assess health-related quality of life.
• Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA [ Time Frame: Baseline, Week 52 ]
• Number of Participants with a Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) [ Time Frame: Baseline up to Week 104 ]

Original Secondary Outcome Measures (submitted: October 14, 2021)

• Part 1: Quantity of Micro-Dystrophin Protein Expression at Week 12 as Measured by Western Blot, in a Subset of Participants [ Time Frame: Week 12 ]
• Part 1: Change From Baseline in Time to Rise From the Floor, Time to Complete 100 and 10 meter Walk/Run, and the Timed Stair Ascend 4 Steps Test at Week 52 [ Time Frame: Baseline, Week 52 ]
• Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) Measured by a Wearable Device [ Time Frame: Baseline up to Week 52 ]
• Part 1: Change from Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score per Domain at Week 52 [ Time Frame: Baseline, Week 52 ]
  PROMIS is a family of instruments developed and validated to assess health-related quality of life. Parents will be asked "Taking into account all aspects of your child's observable symptoms, physical ability, ability to perform daily activities and overall health, how would you rate the change in clinical status for your child since the study start? using the following rating scale 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse."
• Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA [ Time Frame: Baseline up to Week 52 ]
• Number of Participants with a Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) [ Time Frame: Baseline up to Week 52 ]

• 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 Participants With Duchenne Muscular Dystrophy (DMD)
• Official Title: A Phase 3 Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Delivery Study to Evaluate the Safety and Efficacy of SRP-9001 in Subjects With Duchenne Muscular Dystrophy (EMBARK)
• Brief Summary: The study will evaluate the safety and efficacy of gene transfer therapy in boys with DMD. It is a randomized, double-blind, placebo-controlled study. The participants who are randomized to the placebo arm will have an opportunity for treatment with gene transfer therapy at the beginning of the second year.
• 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 intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at Year 2.
  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 Year 2.
  Interventions:

  • Genetic: delandistrogene moxeparvovec
  • Genetic: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 2, 2022): 126
• Original Estimated Enrollment (submitted: October 14, 2021): 120
• Estimated Study Completion Date: November 30, 2024
• Actual Primary Completion Date: October 4, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Is ambulatory and from 4 to under 8 years of age at time of randomization.
• Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• 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).
• 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), with the exception of mutation fully contained within exon 45.

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: 4 Years to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Germany, Hong Kong, Italy, Japan, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05096221
• Other Study ID Numbers: SRP-9001-301; 2019-003374-91 ( 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: November 2023