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
- Conditions
- Duchenne muscular dystrophyTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2022-003407-15-ES
- Lead Sponsor
- Sarepta Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 6
1. Is male at birth, ambulatory, and = 4 to = 8 years of age at the time of Screening.
2. Has a definitive diagnosis of DMD prior to Screening based on documentation of clinical findings and 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.
a. Mutations between or including exons 1-17 are not eligible.
b. In-frame deletions, in-frame duplications, and variants of uncertain significance (VUS”) are not eligible.
3. Able to cooperate with motor assessment testing.
4. Is up to date with all regionally recommended immunizations for encapsulated organisms.
5. Stable dose of oral corticosteroids for at least 12 weeks before Screening and the dose is expected to remain constant (except for potential modifications to accommodate changes in weight) up to Week 52 of the study.
6. Has rAAVrh74 antibody results at Screening that are reactive by the Elecsys® anti AAVrh74 assay.
7. Subjects who are sexually active must agree to use, for the entire duration of the study, a condom and the female sexual partner must also use a medically acceptable form of birth control (eg, oral contraceptive). Refer to Section 16.1 for guidance on highly effective contraceptive methods.
8. If under the age of consent (< 18 years old) has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with the study visit schedule and all other protocol requirements.
9. Is willing to provide informed assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide written informed consent for the subject to participate in the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
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
1. Previous treatment with imlifidase.
2. High dose IVIG treatment (2 g/kg BW) within 28 days prior to imlifidase treatment.
3. Has left ventricular ejection fraction < 40% on the screening ECHO or clinical signs and/or symptoms of cardiomyopathy.
4. Major surgery within 3 months prior to Day 1 or planned surgery for any time during this study.
5. 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 subject’s ability to comply with the protocol required testing or procedures or compromise the subject’s wellbeing, safety, or clinical interpretability.
6. Has serological evidence of current, chronic, or active human immunodeficiency virus, hepatitis C, or hepatitis B infection.
7. Subjects with a history of major thrombotic events, active peripheral vascular disease, or proven hypercoagulable conditions.
8. Subjects with active tuberculosis
9. Presents or has a history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP.
10. Has a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the subject’s ability to comply with the protocol required testing or procedures or compromise the subject’s wellbeing, safety, or clinical interpretability.
11. Has a symptomatic infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, meningitis, tuberculosis) within 4 weeks prior to Day 1.
12. Demonstrates cognitive delay or impairment that could confound motor development in the opinion of the Investigator.
13. Treatment with any of the following therapies according to the time frames specified:
• 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 study:
o Use a human growth factor
• Within 6 months of Day 1:
o Any investigational medication
o Any treatment designed to increase dystrophin expression (eg, Translarna™).
14. Has received a live virus vaccine within 4 weeks or inactive vaccine within 2 weeks of the Day 1 visit or expects to receive a vaccination during the first 3 months after Day 1.
15. Has abnormal laboratory values considered clinically significant by the Investigator including but not limited to:
• Gamma-glutamyl transferase > 2× upper limit of normal (ULN)
• Total bilirubin > ULN. Note; elevations in total bilirubin confirmed to be due to Gilbert’s syndrome are not exclusionary.
• White blood cell count > 18,500 per µl
• Platelets < lower limit of normal
16. Known hypersensitivity to SRP-9001 or its excipients or to imlifidase or its excipients.
17. Family does not want to disclose subject’s study participation with general practitioner/primary care physician and other medical providers.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method