A Gene Transfer Therapy Study to Evaluate the Safety of and Expression From Delandistrogene Moxeparvovec (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: August 1, 2023
• Sponsor: Sarepta Therapeutics, Inc.
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 6, 2020
• First Posted Date: November 12, 2020
• Last Update Posted Date: August 1, 2023
• Actual Study Start Date: November 23, 2020
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

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

• Part 1: Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12, as Measured by Western Blot [ Time Frame: Baseline, Week 12 ]
• Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot [ Time Frame: Week 12 ]

• Original Primary Outcome Measures (submitted: November 6, 2020): Part 1: Change From Baseline in Quantity of Micro-dystrophin Protein Expression Measured by Western Blot [ Time Frame: Baseline up to Week 12 ]

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

• Vector Shedding, Measured in Urine, Saliva, and Stool Samples Post-Infusion [ Time Frame: Day 1 up to Week 104 ]
• Level of Antibody Titers to Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) [ Time Frame: Day 2 up to Week 156 ]
• 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 156 ]
• Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by Immunofluorescence (IF) Fiber Intensity [ Time Frame: Baseline, Week 12 ]
• Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by IF Percent Dystrophin Positive Fibers (PDPF) [ Time Frame: Baseline, Week 12 ]
• Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF Fiber Intensity: [ Time Frame: Week 12 ]
• Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF PDPF [ Time Frame: Week 12 ]

Original Secondary Outcome Measures (submitted: November 6, 2020)

• Vector Shedding as Measured by Polymerase Chain Reaction in Urine, Saliva and Stool Samples Post-infusion [ Time Frame: Baseline up to Week 260 ]
• Immunogenicity of SRP-9001 as Assessed by Antibody Titers to rAAVrh74 [ Time Frame: Screening up to Week 260 ]
• Incidence of Treatment Emergent Adverse Events (TEAEs), Serious AEs and Adverse Events of Special Interest [ Time Frame: Baseline up to Week 260 ]
• Number of Participants with Clinically Significant Abnormalities in Vital Signs, Physical Examinations, Laboratory Parameters, Electrocardiograms (ECG) and Echocardiograms (ECHO) Findings [ Time Frame: Baseline up to Week 260 ]

• 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 of and Expression From Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
• 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)
• Brief Summary: This is an open-label gene transfer therapy study evaluating the safety of and expression from delandistrogene moxeparvovec in participants with DMD. The maximum participant duration for this study is 156 weeks.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Muscular Dystrophy, Duchenne

Intervention

Genetic: delandistrogene moxeparvovec

Single IV infusion of delandistrogene moxeparvovec

Other Names:

• SRP-9001
• delandistrogene moxeparvovec-rokl
• ELEVIDYS

Study Arms

Experimental: Delandistrogene Moxeparvovec

Participants will receive a single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1.

Intervention: Genetic: delandistrogene moxeparvovec

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: July 28, 2023): 58
• Original Estimated Enrollment (submitted: November 6, 2020): 10
• Estimated Study Completion Date: July 31, 2026
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• For Cohorts 1-7: Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• Cohort 1: Is ambulatory, and ≥4 to <8 years of age at the time of Screening.
• Cohort 2: Is ambulatory, and ≥8 to <18 years of age at the time of Screening.
• Cohort 3: Non-ambulatory per protocol specified criteria at the time of Screening.
• Cohort 4: Is ambulatory and ≥3 to <4 years of age at the time of Screening.
• Cohort 5a: Is ambulatory and ≥4 to <9 years of age.
• Cohort 5b: Non-ambulatory per protocol specified criteria at the time of Screening.
• Cohort 6: Is ambulatory, and ≥2 to <3 years of age at the time of Screening.
• Cohort 7: Non-ambulatory per protocol-specified criteria at the time of Screening.
• Ability to cooperate with motor assessment testing.
• Cohorts 1, 2, 3, 5, and 7 only: Stable dose equivalent of oral glucocorticoids 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.
• Cohorts 4 and 6: 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.
• Genetic mutation inclusion criteria vary by cohort.

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 2 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04626674
• Other Study ID Numbers: SRP-9001-103
• 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: July 2023