Open-label, Phase 3 Gene Delivery Study with SRP-9003 in LGMD 2E/R4 Subjects
- Conditions
- imb-girdle muscular dystrophy, type 2E/R4 (LGMD2E/R4) or ß-sarcoglycanopathyMedDRA version: 20.0Level: SOCClassification code: 10010331Term: Congenital familial and genetic disorders Class: 21Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- CTIS2022-503112-17-00
- Lead Sponsor
- Sarepta Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 15
Cohort 1, only ambulatory subjects - = 4 years of age - Able to walk without assistive aid - 10MWT < 30 seconds - NSAD total score = 25, Cohort 2, only non-ambulatory subjects - = 4 years of age - 10MWT = 30 seconds or unable to perform - PUL 2.0 entry scale score = 3, Has AAVrh74 antibody titers < 1:400 (ie, not elevated) as determined by AAVrh74 Antibody ELISA., Is willing to provide informed consent. Alternatively, is willing to provide assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide informed consent for the subject to participate in the study., Willing and able to comply with the study protocol required assessments, Possesses 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic ß-SG DNA gene mutations as documented prior to Screening. Results to be confirmed by Sponsor at a CLIA/CAP/ISO15189 certified laboratory prior to dosing., Able to cooperate with muscle testing, Male or female who are of childbearing potential must agree to use, through Month 24, a highly-effective method of contraception (Appendix 1)., Section 11.4.1.1). A woman is considered of childbearing potential (i.e., fertile) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy., Stable dose equivalent of oral glucocorticoids for at least 12 weeks before Screening/Baseline and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study
Has a symptomatic infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks before study treatment infusion (in such case, enrollment may be postponed). If symptomatic infection occurs between Day -7 (±3d) baseline testing and infusion baseline Day 1, the baseline Day -7 (±3d) testing will need to be repeated., Any contraindication to the use of glucocorticoids., Has hypersensitivity to any component of the study drug, Major surgery within 3 months prior to Day 1 or planned surgery or procedure that would interfere with the conduct of the study for any time during this study, Treatment with any of the following therapies according to the time frames specified • Any time: - Gene therapy - Cell based therapy (eg, stem cell transplantation) - Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), or any other form of gene editing • Within 3 months of Day 1: - Use of human growth factor • Within 6 months of the Screening/Baseline visit: Any investigational medication (other than glucocorticoids), Has received a live virus vaccine within 4 weeks or an inactive vaccine (including a coronavirus disease vaccine) within 2 weeks of the Day 1 visit or expects to receive a vaccine during the first 3 months after Day 1., Has LVEF < 40% on the Screening/Baseline ECHO or clinical signs and/or symptoms of cardiomyopathy, Has FVC = 40% of predicted value at Screening/Baseline and/or requirement for nocturnal ventilation., Serological evidence of current, chronic, or active human immunodeficiency virus infection, or hepatitis B or C infection or active viral or bacterial infection based on clinical observations., Diagnosis of (or ongoing treatment for) an autoimmune disease and on active immunosuppressant treatment., Has abnormal laboratory values considered clinically significant by the Investigator upon medical review including but not limited to: - Gamma-glutamyl transferase upper limit normal (ULN) - Total bilirubin ULN. Note that elevations on total bilirubin due to Gilbert’s syndrome are not exclusionary. - White blood cell count - Platelets, Presence of any other clinically significant illness or medical condition, including cardiac, hepatic, renal, hematologic, immunologic, neuromuscular (other than LGMD2E/R4), 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 subject’s ability to comply with the protocol required testing or procedures or compromise the subject’s wellbeing, safety, or clinical interpretability., Orthopedic comorbidity, such as scoliosis or joint contractures in the upper or lower extremity that would significantly inhibit accurate motor function testing, in the opinion of the Investigator.
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 effect of SRP-9003 on ß-sarcoglycan (ß-SG) expression at Day 60 post-dose as measured by immunofluorescence (IF) percent ß-SG positive fibers (PßSGPF);Secondary Objective: To evaluate the effect of SRP-9003 on ß-SG expression at Day 60 post-dose as measured by IF percent fluorescent expression (PFE) and Western of biopsied muscle tissue, To evaluate the effect of SRP-9003 on physical function through Month 60 in all cohorts, as assessed by: - North Star Assessment for Dysferlinopathy (NSAD) score - Performance of Upper Limb (PUL) 2.0 score, To evaluate the effect of SRP-9003 timed function tests for subjects in Cohort 1 (ambulatory) through Month 60, To evaluate the safety of SRP-9003, To evaluate the effect of SRP-9003 on creatine kinase (CK) level, To evaluate the effect of SRP-9003 on disease milestones (eg, loss of ambulation [LOA]);Primary end point(s): Change from Baseline in ß-SG expression at Day 60 post-dose as measured by IF PßSGPF
- Secondary Outcome Measures
Name Time Method