Muscular Dystrophies, Limb-Girdle
Conditions
Keywords
SRP-9005, Type 2C/R5, LGMD2C/R5, Pediatric, Non-ambulatory, Ambulatory, Phase 1, Phase 3
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.
Interventions
BIOLOGICALSRP-9005
Solution for single IV infusion
DRUGCorticosteroid
Oral tablet (prophylactic)
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study comprises 2 parts: Part A is the Phase 1 portion, Part B is the Phase 3 expansion portion.
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 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 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 Expiratory Volume in 1 Second (FEV1) | 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 % 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 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 North Star Assessment for Dysferlinopathy (NSAD) Total Score | Baseline through Month 60 |
Countries
United States
Outcome results
None listed