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 (HORIZON)

Sarepta Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Duchenne Muscular Dystrophy

Treatments: Procedure: Plasmapheresis; Genetic: delandistrogene moxeparvovec

Study type: Interventional

Funder types: Industry

Identifiers

NCT06597656

SRP-9001-105

Details and patient eligibility

About

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.

Enrollment: 16 estimated patients

Sex: Male

Ages: 4 to 8 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

Delandistrogene Moxeparvovec After Plasmapheresis Procedure

Experimental group

Description:

Participants will receive a single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1 after plasmapheresis procedure if AAVrh74 antibodies are sufficiently low.

Treatment:

Genetic: delandistrogene moxeparvovec

Procedure: Plasmapheresis