Duchenne Muscular Dystrophy
Conditions
Keywords
Gene-Delivery, DMD, Ambulatory, Pediatric, Duchenne, Pre-existing antibodies, rAAVrh74 Antibody, Seropositive, Seropositivity, Titer
Brief summary
This is a gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec and delandistrogene moxeparvovec dystrophin expression in association with imlifidase, in participants with DMD with pre-existing antibodies to rAAVrh74 over a period of 104 weeks.
Interventions
GENETICdelandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec
BIOLOGICALimlifidase
IV infusion of Imlifidase
Sponsors
Hansa Biopharma AB
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to 9 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 confirmatory genetic testing. * Ability to cooperate with motor assessment testing. * Has elevated rAAVrh74 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. * 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
* Previous treatment with imlifidase. * 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 receiving the study drugs 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 Protein Expression as Measured by Western Blot Adjusted by Muscle Content | 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 |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Imlifidase | Up to Day 7 |
| Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) | Up to Week 104 |
| Total IgG in Serum After Imlifidase Administration | Up to Week 12 |
| rAAVrh74 Antibody Titers After Imlifidase Administration | Up to Hour 120 |
| Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Serum, After Delandistrogene Moxeparvovec Administration | Up to Day 7 |
Countries
Spain
Outcome results
None listed