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)

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)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Muscular Dystrophy, Duchenne
• Intervention / Treatment: Genetic: delandistrogene moxeparvovec

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95616
      • University of California, Davis
  • Missouri
    • Saint Louis, Missouri, United States, 21205
      • Washington University in St. Louis
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delandistrogene Moxeparvovec; Participants will receive a single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1.	Genetic: delandistrogene moxeparvovec; Single IV infusion of delandistrogene moxeparvovec; Other Names: SRP-9001; delandistrogene moxeparvovec-rokl; ELEVIDYS

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Vector Shedding, Measured in Urine, Saliva, and Stool Samples Post-Infusion	Day 1 up to Week 104
Level of Antibody Titers to Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74)	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	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	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)	Baseline, Week 12
Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF Fiber Intensity:	Week 12
Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF PDPF	Week 12

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Collaborators: Hoffmann-La Roche
• Investigators: Study Director: Medical Director, Sarepta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Duchenne Muscular Dystrophy; DMD; Dystrophin; Gene-Delivery; Ambulatory Non-ambulatory
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: SRP-9001-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No