Duchenne Muscular Dystrophy
Conditions
Keywords
Gene-Delivery, DMD, Ambulatory, Pediatric, Duchenne, Seropositive, Pre-existing antibodies, AAVrh74 antibody, Plasmapheresis, Titer, Seropositivity
Brief summary
This is a gene transfer therapy study evaluating the safety of and delandistrogene moxeparvovec dystrophin protein expression from delandistrogene moxeparvovec following therapeutic plasma exchange (plasmapheresis) in ambulatory male participants with DMD and pre-existing antibodies to AAVrh74 over a period of 59 weeks.
Interventions
GENETICdelandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec
PROCEDUREPlasmapheresis
Therapeutic plasma exchange procedure
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to 8 Years
Healthy volunteers
No
Inclusion criteria
* Ambulatory per protocol specified criteria. * Has a definitive diagnosis of DMD prior to Screening based on documentation of clinical findings and prior confirmatory genetic testing. * Ability to cooperate with motor assessment testing. * Has elevated AAVrh74 antibody titers per protocol-specified requirements. * A pathogenic frameshift mutation, nonsense mutation or premature stop codon or pathogenic variant in the DMD gene that is expected to lead to absence of dystrophin protein with exception of a mutation in exon 8 and/or 9. * 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).
Exclusion criteria
* Has reduced left ventricular ejection fraction on the screening ECHO or clinical signs and/or symptoms of cardiomyopathy. * Presence of any other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for gene transfer or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability. * Exposure to gene therapy, investigational medication, or other protocol-specified treatment within the protocol specified time limits. * Abnormality in protocol-specified diagnostic evaluations or laboratory tests. . Note: Other inclusion or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression Adjusted by Muscle Content Biopsied Muscle as Measured by Western Blot | Baseline, Week 12 |
| Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by Immunofluorescence (IF) Fiber Intensity | Baseline, Week 12 |
| Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by IF Percent Dystrophin-positive Fibers (PDPF) | Baseline, Week 12 |
| Mean Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Muscle Tissue Biopsy, After Delandistrogene Moxeparvovec Administration | Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) | Baseline up to End of Study (Up to Week 59) |
| Change from Baseline in rAAVrh74 Antibody Titers | Baseline, Week 1 |
Countries
United States
Outcome results
None listed