Clinical trial NCT06241950: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Imlifidase Infusion in Participants With Duchenne Muscular Dystrophy (DMD) Determined to Have Pre-existing Antibodies to Recombinant Adeno-Associated Virus Serotype (rAAVrh74)
Official title: An Open-Label, Systemic Gene Delivery Study to Evaluate the Safety, Tolerability and Expression of SRP-9001 in Association With Imlifidase in Subjects With Duchenne Muscular Dystrophy With Pre-existing Antibodies to rAAVrh74
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Keywords: Gene-Delivery
DMD
Ambulatory
Pediatric
Duchenne
Pre-existing antibodies
rAAVrh74 Antibody
Seropositive
Seropositivity
Titer
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hansa Biopharma AB
First posted: 2024-02-05
Enrollment: 6
Sex: MALE
Minimum age (years): 4
Maximum age (years): 9
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 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.


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 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 exclusion criteria could apply.

Primary outcomes:
measure: Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content
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: Maximum Observed Plasma Concentration (Cmax) of Imlifidase
timeFrame: Up to Day 7
measure: Total IgG in Serum After Imlifidase Administration
timeFrame: Up to Week 12
measure: rAAVrh74 Antibody Titers After Imlifidase Administration
timeFrame: Up to Hour 120
measure: Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Serum, After Delandistrogene Moxeparvovec Administration
timeFrame: Up to Day 7
measure: Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE)
timeFrame: Up to Week 104
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: