A Study of SRP-9005 in Limb Girdle Muscular Dystrophy Type 2C/R5 Pediatric and Adult Participants
Phase 3
Not yet recruiting
- Conditions
- Muscular Dystrophies, Limb-Girdle
- Interventions
- Drug: Corticosteroid
- Registration Number
- NCT06952686
- Lead Sponsor
- Sarepta Therapeutics, Inc.
- Brief Summary
This is a study of a single systemic dose of SRP-9005 in pediatric and adult participants with limb girdle muscular dystrophy type 2C/R5 (LGMD2C/R5). It is comprised of 2 parts (Part A, Part B) that will assess safety and efficacy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 15
Inclusion Criteria
- Ambulatory, defined as able to walk without assistive aid, 10MWR <30 seconds, and NSAD total score ≥20
- Non-ambulatory, defined as 10MWR ≥30 seconds or unable to perform, and PUL 2.0 entry scale score ≥3
- Possess 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic gamma-SG deoxyribonucleic acid (DNA) gene mutations as documented prior to pre-Infusion screening. Results to be confirmed by sponsor at a CLIA/CAP/ISO15189 certified laboratory prior to dosing.
- Have AAVrh74 antibody titers <1:400 (that is, not elevated) as determined by an enzyme-linked immunoassay
Key
Exclusion Criteria
- Has a symptomatic infection (for example, upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks before study treatment infusion
- Part A: Has left ventricular ejection fraction (LVEF) <50% on the screening echocardiogram (ECHO) (without use of cardiac medication) or clinical signs and/or symptoms of cardiomyopathy or any history of cardiac disease
- Part B: Has LVEF <40% on the screening ECHO or clinical signs and/or symptoms of cardiomyopathy
- Has FVC <40% of predicted value at screening 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
- Any prior treatment with gene therapy, cell-based therapy (for example, stem cell transplantation), clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), or any other form of gene editing
- Treatment with human growth factor within 3 months of Day 1
- Treatment with any investigational medication within 6 months of the screening visit
- Is unable to undergo or tolerate a cardiac MRI procedure for any reason
Note: Other inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SRP-9005 SRP-9005 Participants will receive a single intravenous (IV) infusion of SRP-9005. SRP-9005 Corticosteroid Participants will receive a single intravenous (IV) infusion of SRP-9005.
- Primary Outcome Measures
Name Time Method Part A : Number of Participants with Treatment-emergent Adverse Events (TEAEs) Baseline through Month 60 Part A and B: Change from Baseline in gamma-Sarcoglycan (SG) Expression at Day 60 Post-dose in Ambulatory Participants as Measured by Immunofluorescence (IF) Percent Positive Fibers (PPF) Baseline, Day 60
- Secondary Outcome Measures
Name Time Method Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Expiratory Volume in 1 Second % Predicted (FEV1%p) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Peak Expiratory Flow Rate (PEFR) Baseline through Month 60 Part A and B: Change from Baseline through Month 60 in Pulmonary Functions as Assessed by Maximal Inspiratory Pressure (MIP) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Percent Predicted Maximal Inspiratory Pressure (MIP%p) Baseline through Month 60 Part A and B: Change from Baseline through Month 60 in Pulmonary Functions as Assessed by Maximal Expiratory Pressure (MEP) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Percent Predicted Maximal Expiratory Pressure (MEP%p) Baseline through Month 60 Part B: Number of Participants with TEAEs Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in North Star Assessment for Dysferlinopathy (NSAD) Total Score Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Performance of the Upper Limb (PUL) Version 2.0 Total Score Baseline through Month 60 Part A and B: Change from Baseline through Month 60 in Time to Rise From Floor Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Time to Ascend 4 Steps Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Time to Complete the 10-meter Walk/Run (10MWR) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Time to Complete 100-meter Walk/Run (100MWR) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Timed Up and Go Baseline through Month 60 Part A and B: Change from Baseline in gamma-SG Expression at Day 60 in Ambulatory Participants Post-dose as Measured by IF Percent Fiber Intensity (PFI) Baseline, Day 60 Part A and B: Change from Baseline in gamma-SG Expression at Day 60 in Ambulatory Participants Post-dose as Measured by Western Assay Baseline, Day 60 Part A and B: Change from Baseline to Day 60 in Quantity of gamma-SG Protein Expression in Non-ambulatory Participants as Measured by IF PPF Baseline to Day 60 Part A and B: Change from Baseline to Day 60 in Quantity of gamma-SG Protein Expression in Non-ambulatory Participants as Measured by IF PFI Baseline to Day 60 Part A and B: Change from Baseline to Day 60 in Quantity of gamma-SG Protein Expression in Non-ambulatory Participants as Measured by Western Assay Baseline to Day 60 Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by IF PPF Baseline to Month 24 Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by IF PFI Baseline to Month 24 Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by Western Assay Baseline to Month 24 Part A and B: Change from Baseline Through Month 60 in Creatine Kinase Levels Baseline through Month 60 Part A and B: Loss of Ambulation Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Skeletal Muscle Magnetic Resonance Imaging (MRI) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Wearable Device Stride Velocity 95th Percentile (SV95C) (Ambulatory Participants Only) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity (FVC) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity Percent Predicted (FVC%p) Baseline through Month 60 Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Expiratory Volume in 1 Second (FEV1) Baseline through Month 60