Study to assess the safety and expression of RO7494222 (SRP-9001) in participants under the age of 4 with Duchenne muscular dystrophy

Phase 1

Conditions: Duchenne Muscular Dystrophy
MedDRA version: 20.1Level: PTClassification code 10052655Term: Duchenne muscular dystrophy gene carrierSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2022-000691-19-FR

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 21

Inclusion Criteria

•Signed Informed Consent Form
•Signed Assent Form when appropriate, as determined by patient's age and individual site and country standards
•Male at birth
•Meets the following age requirements at the time of study drug infusion:
– For Cohort A: 3 years of age
– For Cohort B: 2 years of age
– For Cohort C: >6 months to <2 years of age
– For Cohort D: =6 months of age
Note: To ensure that cohort-specific age criteria are met at the time of dosing, at the time of signing the Informed Consent Form participants should be approximately one month younger than the maximum age to qualify for a cohort that is actively enrolling.
•Has a definitive diagnosis of DMD prior to screening based on documentation of clinical findings and prior confirmatory genetic testing using a clinical diagnostic genetic test. Genetic report must describe a frameshift deletion, frameshift duplication, premature stop (nonsense), canonical splice site mutation, or other pathogenic variant in the DMD gene fully contained between exons 18 to 79 (inclusive) that is expected to lead to absence of dystrophin protein.
– Mutations between or including exons 1-17 are not eligible.
– In-frame deletions, in-frame duplications, and variants of uncertain significance (VUS”) are not eligible.
•Has rAAVrh74 antibody titers <1:400 (i.e., not elevated) as determined by an ELISA.
•Able to cooperate with age-appropriate motor assessment testing in the opinion of the investigator.
•Has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with the study visit schedule and all protocol requirements.

Are the trial subjects under 18? yes
Number of subjects for this age range: 21
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Receiving regular oral corticosteroids as a treatment for DMD or planning to receive oral corticosteroids as a treatment for DMD within 1 year of baseline.
•Major surgery within 3 months prior to Day 1 or planned surgery during Part 1 of the study.
•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 or known severe allergies that creates unnecessary risks to participate in the study in the opinion of the investigator.
•Known hypersensitivity to delandistrogene moxeparvovec or any excipients of the formulation.
•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 well-being or safety, or clinical interpretability.
•LVEF <50% on the screening echocardiogram (ECHO) or clinical signs and/or symptoms of cardiomyopathy
•Known contact with acute or active hepatitis within 12 weeks or known contact with an infected person (e.g., suspected Epstein-Barr virus [EBV], Varicella zoster virus [VZV], parvovirus B19, human herpes virus 6, and cytomegalovirus [CMV]) within 6 weeks prior to Day 1
•Symptomatic infection (e.g., upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks prior to Day 1.
•Positive COVID-19 test (antigen or PCR) on Day 1 prior to infusion
•Cohort A and B: Positive serology testing for HIV 1 and/or 2, hepatitis C, or hepatitis B
•Cohort C and D:
– Born prematurely (before completion of gestation at 37 weeks) or relevant pregnancy complications in the opinion of the investigator
– Participant’s mother: Serological evidence of current, chronic, or active human immunodeficiency virus (HIV 1 and or 2), hepatitis B, or hepatitis C infection
– Participant’s mother if breastfeeding:
o Clinical signs of acute CMV infection with confirmation by CMV PCR (saliva or urine)
o Clinically significant abnormal liver function (GGT, AST, ALT, ALP, total bilirubin, GLDH) indicative of infectious hepatitis
o Clinically significant illness or acute infection indicative of hepatotropic virus infection (e.g., CMV, EBV, VZV, etc) within 6 weeks prior to Day 1
o Known contact with an infected person with acute or active hepatitis within 12 weeks prior to Day 1
•Demonstrates cognitive delay or impairment that could confound motor development in the opinion of the investigator.
•Treatment with any of the following therapies during the specified time periods:
– Any time:
o Gene therapy
o Cell-based therapy (e.g., stem cell transplantation)
o CRISPR/Cas9, or any other form of gene editing
– Within 12 weeks of Day 1 and any time during the study:
o Use of human growth factor or vamorolone
– Within 6 months of Day 1 and any time during the study:
o Any investigational medication
o Any treatment designed to increase dystrophin expression (e.g., Translarna™, EXONDYS 51™, VILTEPSO™)
•Has received a live virus vaccine or mRNA vaccine within 4 weeks or inactive vaccine within 2 weeks of the Day 1 visit, or expects to receive a vaccination that cannot be reasonably delayed to accommodate concomitant corticosteroid administration during the first 3 months after Day 1.
•Has abnormal laboratory values considered clinically significant including but not limited to:
– GGT >2 xupper limit of norm

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of delandistrogene moxeparvovec;Secondary Objective: To evaluate micro-dystrophin expression from delandistrogene moxeparvovec at 12 weeks as measured by Western blot of biopsied muscle tissue;Primary end point(s): •Incidence of treatment-emergent adverse events<br>•Incidence of serious adverse events<br>•Incidence of adverse events of special interest<br>•Clinically significant changes in vital signs and physical examination findings<br>•Clinically significant changes in safety laboratory assessments, ECGs, and ECHOs<br>;Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change in quantity of micro-dystrophin protein expression from baseline to Week 12 as measured by Western blot;Timepoint(s) of evaluation of this end point: At baseline and at Week 12

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