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)

• ClinicalTrials.gov Identifier: NCT05876780
• Recruitment Status: Active, not recruiting
• First Posted: May 25, 2023
• Last Update Posted: September 21, 2023
• Sponsor: Sarepta Therapeutics, Inc.
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Limb Girdle Muscular Dystrophy	Genetic: SRP-9003	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 19, 2022
• Estimated Primary Completion Date: August 28, 2028
• Estimated Study Completion Date: August 28, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: SRP-9003; Participants will receive single IV infusion of SRP-9003 on Day 1.	Genetic: SRP-9003; Single IV infusion of SRP-9003; Other Name: scAAVrh74.MHCK7.hSGCB

Outcome Measures

Primary Outcome Measures :

1. Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Month 60 ]
2. Change from Baseline in β-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60 [ Time Frame: Baseline, Day 60 ]
3. Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Day 60 [ Time Frame: Baseline, Day 60 ]
4. Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Day 60 [ Time Frame: Baseline, Day 60 ]

Secondary Outcome Measures :

1. Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24 [ Time Frame: Baseline, Month 24 ]
2. Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24 [ Time Frame: Baseline, Month 24 ]
3. Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24 [ Time Frame: Baseline, Month 24 ]
4. Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60 [ Time Frame: Baseline, Month 60 ]
5. 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 [ Time Frame: Baseline, Month 60 ]
6. Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60 [ Time Frame: Baseline, Month 60 ]
7. Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at Month 60 [ Time Frame: Baseline, Month 60 ]
8. Cohort 1 (Ambulatory): Change from Baseline in Stride Velocity (95%) and Stair-climbing Velocity (95%) as Assessed by a Wearable Device at Month 60 [ Time Frame: Baseline, Month 60 ]
9. Cohort 1 (Ambulatory): Change from Baseline in Number of Stairs Climbed per Hour as Assessed by a Wearable Device at Month 60 [ Time Frame: Baseline, Month 60 ]
10. Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60 [ Time Frame: Baseline, Month 60 ]
11. Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60 [ Time Frame: Baseline, Month 60 ]
12. Change from Baseline in Upper Extremity Activity at Month 60 [ Time Frame: Baseline, Month 60 ]
13. Change from Baseline in Angular Wrist Velocity at Month 60 [ Time Frame: Baseline, Month 60 ]
14. Change from Baseline in Vector Genome Copies Using Droplet Digital Polymerase Chain Reaction (ddPCR) in the Target Muscle Tissue [ Time Frame: Baseline, Day 60 and Month 24 ]

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

Sarepta Therapeutics, Inc.

Investigators

• Study Director: Medical Director; Sarepta Therapeutics, Inc.

More Information

• Responsible Party: Sarepta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05876780
• Other Study ID Numbers: SRP-9003-102
• First Posted: May 25, 2023
• Last Update Posted: September 21, 2023
• Last Verified: September 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sarepta Therapeutics, Inc.:

Ambulatory; Non-ambulatory; Gene-Delivery; LGMD2E/R4; β-SG deficiency; LGMD; Performance of Upper Limb (PUL)

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn