Back to resultsA 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)
Primary Purpose
Limb Girdle Muscular Dystrophy
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SRP-9003
Sponsored by
About this trial
This is an interventional treatment trial for Limb Girdle Muscular Dystrophy focused on measuring Ambulatory, Non-ambulatory, Gene-Delivery, LGMD2E/R4, β-SG deficiency, LGMD, Performance of Upper Limb (PUL)
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.
Sites / Locations
- Nationwide Children's Hospital
- St. Jude Children's Research Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SRP-9003
Arm Description
Participants will receive single IV infusion of SRP-9003 on Day 1.
Outcomes
Primary Outcome Measures
Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
Change from Baseline in β-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Day 60
Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Day 60
Secondary Outcome Measures
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24
Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24
Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at 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 Test
Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60
Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at 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 60
Cohort 1 (Ambulatory): Change from Baseline in Number of Stairs Climbed per Hour as Assessed by a Wearable Device at Month 60
Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60
Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60
Change from Baseline in Upper Extremity Activity at Month 60
Change from Baseline in Angular Wrist Velocity at Month 60
Change from Baseline in Vector Genome Copies Using Droplet Digital Polymerase Chain Reaction (ddPCR) in the Target Muscle Tissue
Full Information
NCT ID
NCT05876780
First Posted
May 17, 2023
Last Updated
September 18, 2023
Sponsor
Sarepta Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05876780
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 19, 2022 (Actual)
Primary Completion Date
August 28, 2028 (Anticipated)
Study Completion Date
August 28, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Limb Girdle Muscular Dystrophy
Keywords
Ambulatory, Non-ambulatory, Gene-Delivery, LGMD2E/R4, β-SG deficiency, LGMD, Performance of Upper Limb (PUL)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SRP-9003
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of SRP-9003 on Day 1.
Intervention Type
Genetic
Intervention Name(s)
SRP-9003
Other Intervention Name(s)
scAAVrh74.MHCK7.hSGCB
Intervention Description
Single IV infusion of SRP-9003
Primary Outcome Measure Information:
Title
Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame
Baseline up to Month 60
Title
Change from Baseline in β-SG Protein Expression Quantity Assessed by Immunofluorescence (IF) Fiber Intensity at Day 60
Time Frame
Baseline, Day 60
Title
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Day 60
Time Frame
Baseline, Day 60
Title
Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Day 60
Time Frame
Baseline, Day 60
Secondary Outcome Measure Information:
Title
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Fiber Intensity at Month 24
Time Frame
Baseline, Month 24
Title
Change from Baseline in β-SG Protein Expression Quantity Assessed by IF Percent Protein Fibers (PPF) at Month 24
Time Frame
Baseline, Month 24
Title
Change from Baseline in β-SG Protein Expression Quantity Assessed by Western Blot at Month 24
Time Frame
Baseline, Month 24
Title
Change from Baseline in North Star Assessment for Dysferlinopathy (NSAD) at Month 60
Time Frame
Baseline, Month 60
Title
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
Title
Change from Baseline in Performance of Upper Limb Version 2.0 (PUL 2.0) Score at Month 60
Time Frame
Baseline, Month 60
Title
Change from Baseline in Ability Captured Through Interactive Video Evaluation (ACTIVE) - Seated Workspace Volume Task at Month 60
Time Frame
Baseline, Month 60
Title
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
Title
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
Title
Cohort 1 (Ambulatory): Change from Baseline Distance Walked per Hour as Assessed by a Wearable Device at Month 60
Time Frame
Baseline, Month 60
Title
Cohort 1 (Ambulatory): Change from Baseline in Stride Length (95%) as Assessed by a Wearable Device at Month 60
Time Frame
Baseline, Month 60
Title
Change from Baseline in Upper Extremity Activity at Month 60
Time Frame
Baseline, Month 60
Title
Change from Baseline in Angular Wrist Velocity at Month 60
Time Frame
Baseline, Month 60
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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)
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