A Gene Transfer Therapy to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Therapeutic Plasma Exchange (Plasmapheresis) in Participants With Duchenne Muscular Dystrophy (DMD) and Pre-existing Antibodies to AAVrh74

Phase 1

Recruiting

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Genetic: delandistrogene moxeparvovec; Procedure: Plasmapheresis

• Registration Number: NCT06597656
• Lead Sponsor: Sarepta Therapeutics, Inc.

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 58 weeks.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-12
• Study First Submitted QC: 2024-09-12
• Study Start: 2024-09-18
• Study First Posted: 2024-09-19
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-03
• Primary Completion: 2025-11-30
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 16

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 exclusion criteria could apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Delandistrogene Moxeparvovec After Plasmapheresis Procedure	delandistrogene moxeparvovec	Participants will receive a single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1 after plasmapheresis procedure if AAVrh74 antibodies are sufficiently low.
Delandistrogene Moxeparvovec After Plasmapheresis Procedure	Plasmapheresis	Participants will receive a single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1 after plasmapheresis procedure if AAVrh74 antibodies are sufficiently low.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 58)
Change from Baseline in rAAVrh74 Antibody Titers	Baseline, Week 1

Trial Locations

Locations (2)

Washington University School of Medicine in St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States