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

Sponsor

Sarepta Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03652259

Collaborator

(none)

Enrollment

Location

Arms

75.6

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The proposed clinical trial is the first-in-human, single-center, open-label, gene delivery study of SRP-9003 in participants with LGMD2E.

Condition or Disease	Intervention/Treatment	Phase
Limb-Girdle Muscular Dystrophy, Type 2E	Genetic: SRP-9003	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Oct 27, 2018

Anticipated Primary Completion Date :

Feb 14, 2025

Anticipated Study Completion Date :

Feb 14, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: SRP-9003 Participants will receive a single intravenous (IV) infusion of SRP-9003 at a prespecified dose.	Genetic: SRP-9003 SRP-9003 will be administered through a single systemic injection. Other Names: LGMD2E vector
Experimental: Cohort 2: SRP-9003 Participants will receive a single IV infusion of SRP-9003. Dose will be determined based on the findings from Cohort 1.	Genetic: SRP-9003 SRP-9003 will be administered through a single systemic injection. Other Names: LGMD2E vector

Arm

Intervention/Treatment

Experimental: Cohort 1: SRP-9003

Participants will receive a single intravenous (IV) infusion of SRP-9003 at a prespecified dose.

Genetic: SRP-9003

SRP-9003 will be administered through a single systemic injection.

Other Names:

LGMD2E vector

Experimental: Cohort 2: SRP-9003

Participants will receive a single IV infusion of SRP-9003. Dose will be determined based on the findings from Cohort 1.

Genetic: SRP-9003

SRP-9003 will be administered through a single systemic injection.

Other Names:

LGMD2E vector

Outcome Measures

Primary Outcome Measures

Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) [Baseline up to 5 years]

Secondary Outcome Measures

Change From Baseline in Quantity of Beta-Sarcoglycan (β-SG) Protein Expression at Day 60, as Measured by Western Blot [Baseline, Day 60]
β-SG gene expression levels will be quantified by Western Blot and compared between pre and post muscle biopsies.
Change From Baseline in Quantity of β-SG Protein Expression at Day 60, as Measured by Immunofluorescence [Baseline, Day 60]
β-SG gene expression levels will be quantified by immunofluorescence and compared between pre and post muscle biopsies.
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.