Delandistrogene moxeparvovec gene therapy for Duchenne muscular dystrophy
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 trial tests a one-time gene therapy called delandistrogene moxeparvovec in children and young adults with Duchenne muscular dystrophy to try to restore dystrophin production and improve muscle function.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 83 (estimated) |
| Ages | 2 Years and up |
| Sex | Male |
| Sponsor | Sarepta Therapeutics, Inc. Industry-sponsored |
| Locations | 7 sites (Little Rock, Arkansas and 6 other locations) |
| Trial ID | NCT04626674 on ClinicalTrials.gov |
What this trial studies
This is an open-label Phase 1 gene transfer trial focused on the safety of and expression from delandistrogene moxeparvovec in participants with genetically confirmed Duchenne muscular dystrophy. The study enrolls multiple cohorts spanning ambulatory and non-ambulatory participants across pediatric and adolescent age ranges, with cohort-specific entry criteria (including an upper-limb performance requirement for Cohort 8). Participants receive the gene-delivery intervention and are followed for up to 156 weeks for safety, laboratory, and expression endpoints. Enrollment for Cohorts 1–7 is complete and Cohort 8 is currently enrolling at several U.S. academic medical centers.
Who should consider this trial
Good fit: Individuals with a genetically confirmed diagnosis of Duchenne muscular dystrophy who meet the trial's cohort-specific age and ambulatory criteria (including ambulatory and non-ambulatory groups, and the PUL score requirement for Cohort 8) are eligible.
Not a fit: People without a confirmed DMD genetic diagnosis or those who do not meet the protocol's cohort-specific functional or age criteria are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, the treatment could increase dystrophin production and slow or improve muscle weakness in people with DMD.
How similar studies have performed: Related AAV micro-dystrophin gene-delivery programs have shown dystrophin expression and some early functional signals in Phase 1/2 trials, but longer-term clinical benefit and safety are still being determined.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * For Cohorts 1-8: 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 with time to rise from the floor ≤7 seconds at the screening visit. * 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. * Cohort 8: Non-ambulatory per protocol-specified criteria at the time of Screening, has a performance upper limb (PUL) entry item score ≥3 at the Screening visit and has a total PUL score of ≥20 and ≤40 at the time of Screening. * Ability to cooperate with motor assessment testing. * Cohorts 1, 2, 3, 5, 7 and 8 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. * Cohort 8: Any confounding factors that would prevent the use of oral sirolimus including a known hypersensitivity to sirolimus or any of its excipients. Other inclusion/exclusion criteria apply.
Where this trial is running
Little Rock, Arkansas and 6 other locations
- Arkansas Children's Hospital — Little Rock, Arkansas, United States (Recruiting)
- Stanford University — Palo Alto, California, United States (Recruiting)
- University of California, Davis — Sacramento, California, United States (Recruiting)
- Washington University in St. Louis — St Louis, Missouri, United States (Recruiting)
- Nationwide Children's Hospital — Columbus, Ohio, United States (Active_not_recruiting)
- Neurology Rare Disease Center — Flower Mound, Texas, United States (Recruiting)
- Children's Hospital of The King's Daughters — Norfolk, Virginia, United States (Recruiting)
Study contacts
- Study coordinator: Sarepta Therapeutics Inc., For Clinical Trial Information, Select Option 4
- Email: SareptAlly@Sarepta.com
- Phone: 1-888-SAREPTA (1-888-727-3782)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.