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)

Phase 1Active Not RecruitingNCT05876780

Sarepta Therapeutics, Inc.6 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Limb Girdle Muscular Dystrophy

Interventions

SRP-9003GENETIC

Single IV infusion of SRP-9003

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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 Outcomes

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