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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 1
Active, not recruiting
Conditions
Limb Girdle Muscular Dystrophy
Interventions
Genetic: SRP-9003
Registration Number
NCT05876780
Lead Sponsor
Sarepta Therapeutics, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
6
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SRP-9003SRP-9003Participants will receive single IV infusion of SRP-9003 on Day 1.
Primary Outcome Measures
NameTimeMethod
Change from Baseline in β-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60Baseline, Day 60
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 IF Percent Protein Fibers (PPF) at Day 60Baseline, Day 60
Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Day 60Baseline, Day 60
Secondary Outcome Measures
NameTimeMethod
Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at Month 60Baseline, 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 60Baseline, Month 60
Cohort 1 (Ambulatory): Change from Baseline in Number of Stairs Climbed per Hour as Assessed by a Wearable Device at Month 60Baseline, Month 60
Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60Baseline, 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 TestBaseline, Month 60
Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60Baseline, Month 60
Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60Baseline, Month 60
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24Baseline, Month 24
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24Baseline, Month 24
Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24Baseline, Month 24
Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60Baseline, Month 60
Change from Baseline in Upper Extremity Activity at Month 60Baseline, Month 60
Change from Baseline in Angular Wrist Velocity at Month 60Baseline, Month 60
Change from Baseline in Vector Genome Copies Using Droplet Digital Polymerase Chain Reaction (ddPCR) in the Target Muscle TissueBaseline, Day 60 and Month 24

Trial Locations

Locations (2)

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

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