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)

Overview

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.

Full Title of Study: “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)”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: January 31, 2026

Interventions

• Genetic: SRP-9003
  • Single IV infusion of SRP-9003

Arms, Groups and Cohorts

• Experimental: SRP-9003
  • Participants will receive single IV infusion of SRP-9003 on Day 1.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

• Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24
  • Time Frame: Baseline, Month 24
• Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24
  • Time Frame: Baseline, Month 24
• Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24
  • Time Frame: Baseline, Month 24
• Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60
  • Time Frame: 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
  • Time Frame: Baseline, Month 60
• Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60
  • Time Frame: Baseline, Month 60
• Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) – Seated Workspace Volume Task at Month 60
  • Time Frame: 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
  • Time Frame: 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
  • Time Frame: Baseline, Month 60
• Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60
  • Time Frame: Baseline, Month 60
• Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60
  • Time Frame: Baseline, Month 60
• Change from Baseline in Upper Extremity Activity at Month 60
  • Time Frame: Baseline, Month 60
• Change from Baseline in Angular Wrist Velocity at Month 60
  • Time Frame: Baseline, Month 60
• Change from Baseline in Vector Genome Copies Using Droplet Digital Polymerase Chain Reaction (ddPCR) in the Target Muscle Tissue
  • Time Frame: Baseline, Day 60 and Month 24

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 4 Years

Maximum Age: 50 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Sarepta Therapeutics, Inc.
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Medical Director, Study Director, Sarepta Therapeutics, Inc.