Gene Delivery Clinical Trial of SRP-9003 (Bidridistrogene Xeboparvovec) for Participants With Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E) (Beta-Sarcoglycan Deficiency)

Study Overview
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Brief Summary
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The proposed clinical trial is the first-in-human, single-center, open-label, gene delivery study of SRP-9003 (bidridistrogene xeboparvovec) in participants with LGMD2E.

Official Title
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A Single-Center, Open-Label, Systemic Gene Delivery Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9003 Administered by Systemic Infusion in Subjects With LGMD2E (β-Sarcoglycan Deficiency)

Conditions
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Limb-Girdle Muscular Dystrophy, Type 2E

Intervention / Treatment
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* Genetic: SRP-9003


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Males or females of any ethnic group β-SG deoxyribonucleic acid (DNA) gene mutations at both alleles Weakness demonstrated based on history of difficulty in running, jumping and climbing stairs A 100 meter walk/run (MWR) test result: ≥40 % of predicted for age-, height-, gender-, and weight-matched healthy controls at the screening visit EXCLUSION CRITERIA Active viral infection based on clinical observations Cardiac magnetic resonance imaging (MRI) determined left ventricular ejection fraction (LVEF) <40% Serological evidence of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection Diagnosis of (or ongoing treatment for) an autoimmune disease Abnormal laboratory values considered clinically significant Concomitant illness or requirement for chronic drug treatment that, in the opinion of the Principal Investigator, creates unnecessary risks for gene transfer. Other inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 15 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: SRP-9003<br>Participants will receive a single intravenous (IV) infusion of SRP-9003 at a prespecified dose. | Genetic: SRP-9003<br>* SRP-9003 will be administered through a single systemic injection.<br>* Other names: bidridistrogene xeboparvovec;|
| Experimental: Cohort 2: SRP-9003<br>Participants will receive a single IV infusion of SRP-9003. Dose will be determined based on the findings from Cohort 1. | Genetic: SRP-9003<br>* SRP-9003 will be administered through a single systemic injection.<br>* Other names: bidridistrogene xeboparvovec;|

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 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Quantity of Beta-Sarcoglycan (β-SG) Protein Expression at Day 60, as Measured by Western Blot | β-SG gene expression levels will be quantified by Western Blot and compared between pre and post muscle biopsies. | Baseline, Day 60 | 
| Change From Baseline in Quantity of β-SG Protein Expression at Day 60, as Measured by Immunofluorescence | β-SG gene expression levels will be quantified by immunofluorescence and compared between pre and post muscle biopsies. | Baseline, Day 60 | 
| Change From Baseline in Quantity of β-SG Protein Expression at Day 60, as Measured by Immunohistochemistry Percent B-SG Positive Fibers |  | Baseline, Day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LGMD2E, limb girdle muscular dystrophy, beta-sarcoglycan, gene transfer, adeno-associated virus, LGMDR4