Duchenne Muscular Dystrophy
Conditions
Keywords
DMD, Gene-Delivery, Pediatric, North Star Ambulatory Assessment (NSAA), Performance of Upper Limb (PUL), Duchenne
Brief summary
The study will evaluate the safety and efficacy of delandistrogene moxeparvovec gene transfer therapy in non-ambulatory and ambulatory males with DMD. This is a randomized, double-blind, placebo-controlled 2-part study. Participants will be in the study for approximately 128 weeks. All participants will have the opportunity to receive intravenous (IV) delandistrogene moxeparvovec in either Part 1 or Part 2.
Interventions
GENETICdelandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec
GENETICplacebo
Single IV infusion of matching placebo
Sponsors
Hoffmann-La Roche
Sarepta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing. * Cohort 1 only: Non-ambulatory per protocol-specified criteria. * Cohort 2 only: Ambulatory per protocol-specified criteria and ≥8 to \<18 years of age at the time of Screening. * Ability to cooperate with motor assessment testing. * Stable daily dose of oral corticosteroids for at least 12 weeks prior to Screening, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight). * Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) antibody titers are not elevated as per protocol-specified requirements. * A pathogenic frameshift mutation or premature stop codon in the DMD gene, except for any deletion mutations in exon 8 and/or 9.
Exclusion criteria
* 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. * Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer. Other inclusion or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72 | Baseline, Week 72 |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72 | Baseline, Week 72 |
| Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot | Week 12 |
| Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72 | Baseline, Week 72 |
| Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72 | Baseline, Week 72 |
| Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72 | Baseline, Week 72 |
| Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72 | Baseline, Week 72 |
| Part 1: Change From Baseline in the Middle Domain Score of PUL (Version 2.0) at Week 72 | Baseline, Week 72 |
| Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) | Baseline up to Week 124 |
Countries
Australia, Belgium, Canada, Germany, Hong Kong, Israel, Italy, Japan, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Outcome results
None listed