Clinical trial NCT06597656: 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
Official title: An Open-Label, Systemic Gene Delivery Study to Evaluate the Safety, Tolerability and Expression of Delandistrogene Moxeparvovec Following Plasmapheresis in Subjects With Duchenne Muscular Dystrophy and Pre-existing Antibodies to AAVrh74
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Keywords: Gene-Delivery
DMD
Ambulatory
Pediatric
Duchenne
Seropositive
Pre-existing antibodies
AAVrh74 antibody
Plasmapheresis
Titer
Seropositivity
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 16
Sex: MALE
Minimum age (years): 4
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression Adjusted by Muscle Content Biopsied Muscle as Measured by Western Blot
timeFrame: Baseline, Week 12
measure: Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by Immunofluorescence (IF) Fiber Intensity
timeFrame: Baseline, Week 12
measure: Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by IF Percent Dystrophin-positive Fibers (PDPF)
timeFrame: Baseline, Week 12
measure: Mean Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Muscle Tissue Biopsy, After Delandistrogene Moxeparvovec Administration
timeFrame: Week 12
Secondary outcomes:
measure: Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE)
timeFrame: Baseline up to End of Study (Up to Week 58)
measure: Change from Baseline in rAAVrh74 Antibody Titers
timeFrame: Baseline, Week 1
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: