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)

Sponsor

Sarepta Therapeutics, Inc. (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05876780

Collaborator

(none)

Enrollment

Location

Arm

49.4

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Limb Girdle Muscular Dystrophy	Genetic: SRP-9003	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Dec 19, 2022

Anticipated Primary Completion Date :

Jan 31, 2026

Anticipated Study Completion Date :

Jan 31, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.