Clinical trial NCT05876780: 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)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Limb Girdle Muscular Dystrophy
Keywords: Ambulatory
Non-ambulatory
Gene-Delivery
LGMD2E/R4
β-SG deficiency
LGMD
Performance of Upper Limb (PUL)
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-25
Enrollment: 6
Sex: ALL
Minimum age (years): 4
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Baseline up to Month 60
measure: Change from Baseline in β-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60
timeFrame: Baseline, Day 60
measure: Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Day 60
timeFrame: Baseline, Day 60
measure: Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Day 60
timeFrame: Baseline, Day 60
Secondary outcomes:
measure: Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24
timeFrame: Baseline, Month 24
measure: Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24
timeFrame: Baseline, Month 24
measure: Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24
timeFrame: Baseline, Month 24
measure: Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60
timeFrame: Baseline, Month 60
measure: 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
timeFrame: Baseline, Month 60
measure: Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60
timeFrame: Baseline, Month 60
measure: Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at Month 60
timeFrame: Baseline, Month 60
measure: Cohort 1 (Ambulatory): Change from Baseline in Stride Velocity (95%) and Stair-climbing Velocity (95%) as Assessed by a Wearable Device at Month 60
timeFrame: Baseline, Month 60
measure: Cohort 1 (Ambulatory): Change from Baseline in Number of Stairs Climbed per Hour as Assessed by a Wearable Device at Month 60
timeFrame: Baseline, Month 60
measure: Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60
timeFrame: Baseline, Month 60
measure: Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60
timeFrame: Baseline, Month 60
measure: Change from Baseline in Upper Extremity Activity at Month 60
timeFrame: Baseline, Month 60
measure: Change from Baseline in Angular Wrist Velocity at Month 60
timeFrame: Baseline, Month 60
measure: Change from Baseline in Vector Genome Copies Using Droplet Digital Polymerase Chain Reaction (ddPCR) in the Target Muscle Tissue
timeFrame: Baseline, Day 60 and Month 24
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: