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)

Limb Girdle Muscular Dystrophy Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05876780
• Other study ID #: SRP-9003-102
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 19, 2022
• Est. completion date: August 28, 2028

Study information

• Verified date: September 2023
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. completion date: August 28, 2028
• Est. primary completion date: August 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 50 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Limb Girdle Muscular Dystrophy
• Muscular Dystrophies

Intervention

Genetic:
• SRP-9003
Single IV infusion of SRP-9003

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)		Baseline up to Month 60
Primary	Change from Baseline in ß-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60		Baseline, Day 60
Primary	Change from Baseline in ß-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Day 60		Baseline, Day 60
Primary	Change from Baseline in ß-SG Protein Expression Quantity Assessed by Western Blot at Day 60		Baseline, Day 60
Secondary	Change from Baseline in ß-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24		Baseline, Month 24
Secondary	Change from Baseline in ß-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24		Baseline, Month 24
Secondary	Change from Baseline in ß-SG Protein Expression Quantity Assessed by Western Blot at Month 24		Baseline, Month 24
Secondary	Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60		Baseline, Month 60
Secondary	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
Secondary	Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60		Baseline, Month 60
Secondary	Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at Month 60		Baseline, Month 60
Secondary	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
Secondary	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
Secondary	Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60		Baseline, Month 60
Secondary	Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60		Baseline, Month 60
Secondary	Change from Baseline in Upper Extremity Activity at Month 60		Baseline, Month 60
Secondary	Change from Baseline in Angular Wrist Velocity at Month 60		Baseline, Month 60
Secondary	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