A Gene Transfer Therapy Study to Evaluate the Safety of and Expression From SRP-9001 in Participants With Duchenne Muscular Dystrophy (DMD) (ENDEAVOR)

• ClinicalTrials.gov Identifier: NCT04626674
• Recruitment Status: Enrolling by invitation
• First Posted: November 12, 2020
• Last Update Posted: November 12, 2021
• Sponsor: Sarepta Therapeutics, Inc.
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Study Description

Brief Summary:

This is an open-label gene transfer therapy study evaluating the safety of and expression from SRP-9001 in participants with DMD over 260 weeks.

Condition or disease	Intervention/treatment	Phase
Muscular Dystrophy, Duchenne	Genetic: SRP-9001	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Systemic Gene Delivery Study Using Commercial Process Material to Evaluate the Safety of and Expression From SRP-9001 in Subjects With Duchenne Muscular Dystrophy (ENDEAVOR)
• Actual Study Start Date: November 23, 2020
• Estimated Primary Completion Date: March 31, 2022
• Estimated Study Completion Date: July 30, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: SRP-9001; Participants will receive a single intravenous (IV) infusion of SRP-9001 on Day 1.	Genetic: SRP-9001; Single IV infusion of SRP-9001

Outcome Measures

Primary Outcome Measures :

1. Part 1: Change From Baseline in Quantity of Micro-Dystrophin Protein Expression at Week 12, as Measured by Western Blot [ Time Frame: Baseline, Week 12 ]

Secondary Outcome Measures :

1. Vector Shedding, Measured in Urine, Saliva, and Stool Samples Post-Infusion [ Time Frame: Day 1 up to Week 52 ]
2. Level of Antibody Titers to Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) [ Time Frame: Day 2 up to Week 260 ]
3. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) of Special Interest [ Time Frame: Baseline up to Week 260 ]
4. Change From Baseline in Quantity of Micro-Dystrophin Protein Expression at Week 12, as Measured by Immunofluorescence (IF) Fiber Intensity [ Time Frame: Baseline, Week 12 ]
5. Change From Baseline in Quantity of Micro-Dystrophin Expression at Week 12, as Measured by IF Percent Dystrophin Positive Fibers (PDPF) [ Time Frame: Baseline, Week 12 ]

Eligibility Criteria

• Ages Eligible for Study: 3 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Cohort 1 only: Is ambulatory, and ≥4 to <8 years of age at the time of Screening.
• Cohort 2 only: Is ambulatory, and ≥8 to <18 years of age at the time of Screening.
• Cohort 3 only: Non-ambulatory per protocol specified criteria.
• Cohort 4 only: Is ambulatory, and ≥3 to <4 years of age at the time of Screening.
• Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• Ability to cooperate with motor assessment testing.
• Cohorts 1, 2, and 3 only: Stable dose equivalent of oral corticosteroids for at least 12 weeks before screening and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study.
• Cohort 4: Do not yet require use of chronic steroids for treatment of their DMD, in the opinion of the Investigator, and are not receiving steroids at the time of Screening.
• rAAVrh74 antibody titers are not elevated as per protocol-specified requirements.

Exclusion Criteria:

• Has a concomitant illness, autoimmune disease, chronic drug treatment, and/or cognitive delay/impairment that in the opinion of the Investigator creates unnecessary risks for gene transfer.
• 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.

Other inclusion/exclusion criteria apply.

Contacts and Locations

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94304

University of California, Davis

Sacramento, California, United States, 95616

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 21205

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Virginia

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States, 23507

Sponsors and Collaborators

Sarepta Therapeutics, Inc.

Hoffmann-La Roche

Investigators

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

More Information

• Responsible Party: Sarepta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04626674
• Other Study ID Numbers: SRP-9001-103
• First Posted: November 12, 2020
• Last Update Posted: November 12, 2021
• Last Verified: October 2021

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

Keywords provided by Sarepta Therapeutics, Inc.:

Duchenne Muscular Dystrophy; Gene-Delivery; DMD; Ambulatory; Pediatric; Micro-dystrophin

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked