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)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Limb Girdle Muscular Dystrophy
• Intervention / Treatment: Genetic: SRP-9003

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Investigators: Study Director: Medical Director, Sarepta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2022
• Primary Completion (Estimated): August 28, 2028
• Study Completion (Estimated): August 28, 2028

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gene-Delivery; Ambulatory; LGMD; Performance of Upper Limb (PUL); Non-ambulatory; LGMD2E/R4; β-SG deficiency
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
• Other Study ID Numbers: SRP-9003-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No