Muscular Dystrophy, Duchenne
Conditions
Keywords
Duchenne Muscular Dystrophy, Gene-Delivery, DMD, Ambulatory Non-ambulatory, Pediatric, Dystrophin
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
Enrollment for Cohorts 1 through 7 has been completed. Cohort 8 is currently enrolling new participants.
Interventions
GENETICdelandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec
Sponsors
Sarepta Therapeutics, Inc.
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
2 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 (Cohorts 1 to 5): Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12, as Measured by Western Blot | Baseline, Week 12 |
| Part 1 (Cohorts 6 to 8): Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot | Week 12 |
| Cohort 8: Number of Participants with Acute Liver Injury (ALI) | Baseline up to Week 72 |
Secondary
| 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 of Special Interest (AESIs) | Baseline up to Week 156 |
| Cohort 8: Number of Participants With Infections, Edema, Wound-healing Complications, Hyperlipidemia, Angioedema, and Intestinal Lung Disease/ Non-infectious Pneumonitis | Baseline up to Week 72 |
| 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 |
| Cohort 8: Number of Participants With Hepatic AEs, Hepatic Biomarkers, and Laboratory Assessments Indicative of Either Acute Hepatocellular Injury or Acute Liver Dysfunction | Baseline up to Week 72 |
| Cohort 8: Number of Participants with Severe ALI | Baseline up to Week 72 |
| Cohort 8: Duration of Steroids Administered | Baseline up to Week 72 |
Countries
United States
Contacts
CONTACTSarepta Therapeutics Inc., For Clinical Trial Information, Select Option 4
STUDY_DIRECTORMedical Director
Sarepta Therapeutics, Inc.
Outcome results
None listed