Sarepta ENVISION
A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of SRP- 9001 in Non-Ambulatory and Ambulatory Subjects With Duchenne Muscular Dystrophy (ENVISION)
ENVISION is a large study of SRP-9001 (delandistrogene moxeparvovec) in older ambulatory and non-ambulatory individuals living with Duchenne muscular dystrophy that is intended to support global regulatory approval. The study has a double blind, 72-week placebo control design with crossover. This means that half of the enrolled participants would be dosed with SRP-9001 in the first part of the study while the other half receives placebo. After 72 weeks, each participant will cross over, in other words, they would receive the opposite of what they received originally and observed for an additional 52 weeks.
Primary Outcome Measures
1. Part 1: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72 [ Time Frame: Baseline, Week 72 ]
Secondary Outcome Measures
1. Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72 [ Time Frame: Baseline, Week 72 ]
2. Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72 [ Time Frame: Baseline, Week 72 ]
3. Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot [ Time Frame: Week 12 ]
4. Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72 [ Time Frame: Baseline, Week 72 ]
5. Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) [ Time Frame: Baseline up to Week 124 ]
6. Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72 [ Time Frame: Baseline, Week 72 ]
7. Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72 [ Time Frame: Baseline, Week 72 ]
Can I take part?
Inclusion Criteria
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 contained between exons 18 and 79 (inclusive).
Exclusion Criteria
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 exclusion criteria could apply.
Age
8 - 17 years
Mutation Specific
Muscle Biopsy
Required
Ambulation
both