A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency)

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety of SRP-9003 and to quantify expression of β-SG in the skeletal muscle of participants with limb-girdle muscular dystrophy, type 2E/R4 (LGMD2E/R4). The study will include both ambulatory (Cohort 1) and non-ambulatory (Cohort 2) participants.

Official Title
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A Multicenter, Open-label, Single-dose, Systemic Gene Transfer Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9003 on Subjects With Limb Girdle Muscular Dystrophy, Type 2E/R4 (β-Sarcoglycan Deficiency)

Conditions
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Limb Girdle Muscular Dystrophy

Intervention / Treatment
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* Genetic: SRP-9003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1 only: Ambulatory per protocol specified criteria. - Cohort 2 only: Non-ambulatory per protocol specified criteria and 4 to 50 years of age. Possesses 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic β-sarcoglycan gene Deoxyribonucleic acid (DNA) (SGCB) gene mutations based on documented clinical findings. Ability to cooperate with muscle testing. Exclusion Criteria: Presence of any other clinically significant illness or medical condition, including cardiac, pulmonary, 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 participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability. Exposure to gene therapy, investigational medication, or other protocol-specified treatment within the protocol specified time limits. Any contraindication to use of corticosteroid. Note: Other inclusion or exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRP-9003<br>Participants will receive single IV infusion of SRP-9003 on Day 1. | Genetic: SRP-9003<br>* Single IV infusion of SRP-9003<br>* Other names: scAAVrh74.MHCK7.hSGCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) |  | Baseline up to Month 60 | 
| Change from Baseline in β-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60 |  | Baseline, Day 60 | 
| Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Day 60 |  | Baseline, Day 60 | 
| Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Day 60 |  | Baseline, Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24 |  | Baseline, Month 24 | 
| Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24 |  | Baseline, Month 24 | 
| Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24 |  | Baseline, Month 24 | 
| Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60 |  | Baseline, Month 60 | 
| Change From Baseline in Time to Rise From the Floor, Time to Complete 100 and 10 meter Walk/Run, and the Timed Stair Ascend 4 Steps Test |  | Baseline, Month 60 | 
| Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60 |  | Baseline, Month 60 | 
| Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at Month 60 |  | Baseline, Month 60 | 
| Cohort 1 (Ambulatory): Change from Baseline in Stride Velocity (95%) and Stair-climbing Velocity (95%) as Assessed by a Wearable Device at Month 60 |  | Baseline, Month 60 | 
| Cohort 1 (Ambulatory): Change from Baseline in Number of Stairs Climbed per Hour as Assessed by a Wearable Device at Month 60 |  | Baseline, Month 60 | 
| Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60 |  | Baseline, Month 60 | 
| Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60 |  | Baseline, Month 60 | 
| Change from Baseline in Upper Extremity Activity at Month 60 |  | Baseline, Month 60 | 
| Change from Baseline in Angular Wrist Velocity at Month 60 |  | Baseline, Month 60 | 
| Change from Baseline in Vector Genome Copies Using Droplet Digital Polymerase Chain Reaction (ddPCR) in the Target Muscle Tissue |  | Baseline, Day 60 and Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LGMD, Ambulatory, Non-ambulatory, Gene-Delivery, LGMD2E/R4, β-SG deficiency, Performance of Upper Limb (PUL)