Back to resultsA Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D)
Primary Purpose
Limb-Girdle Muscular Dystrophy, Type 2D
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
SRP-9004
Sponsored by
About this trial
This is an interventional treatment trial for Limb-Girdle Muscular Dystrophy, Type 2D focused on measuring limb girdle muscular dystrophy, LGMD2D, alpha-sarcoglycan, gene transfer, adeno-associated virus
Eligibility Criteria
Key Inclusion Criteria:
- Cohort 1A must be adult and wheelchair-dependent; Cohorts 1B and 2 will be participants of age 7 or older.
- Confirmed alpha-sarcoglycan deficiency or identified sarcoglycan alpha (SGCA) deoxyribonucleic acid (DNA) mutation.
- Participants enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (that is, a Gowers' sign, use a handrail for climbing stairs) and walk ≤80% of predicted distance on the 6 minute walk test (6MWT) based on normative data.
Key Exclusion Criteria:
- Active viral infection based on clinical observations.
- The presence of SGCA mutations without weakness or loss of function.
- Symptoms or signs of cardiomyopathy.
- Serological evidence of human immunodeficiency virus (HIV), Hepatitis B, or C infection.
- Diagnosis of (or ongoing treatment for) an autoimmune disease.
- Participants with AAVrh74 or AAV8 binding antibody titers ≥ 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) immunoassay.
Other inclusion/exclusion criteria apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion)
Cohort 1B Low Dose (Bilateral Limb Perfusion)
Cohort 2 High Dose (Bilateral Limb Perfusion)
Arm Description
Non-ambulant participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to a single limb on Day 0.
Participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to both limbs on Day 0.
Participants with LGMD2D will receive 1 high dose of SRP-9004 via ILI to both limbs on Day 0.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs).
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug related. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Treatment-related Treatment Emergent Adverse Event (TEAE) is defined as an TEAE that was classified by the investigator as related to treatment.
Secondary Outcome Measures
Change From Baseline of the Distance Walked in 6 Minutes (6MWT)
The 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course in 6 minutes (timed), and the distance walked (in meters) was recorded.
Full Information
NCT ID
NCT01976091
First Posted
July 24, 2013
Last Updated
May 17, 2023
Sponsor
Sarepta Therapeutics, Inc.
Collaborators
Nationwide Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01976091
Brief Title
A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D)
Official Title
Phase I/IIA Gene Transfer Clinical Trial for LGMD2D (Alpha-Sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2015 (Actual)
Primary Completion Date
March 14, 2019 (Actual)
Study Completion Date
March 14, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.
Collaborators
Nationwide Children's Hospital
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
This is an open-label, dose escalation gene transfer therapy study evaluating the safety of SRP-9004 (patidistrogene bexoparvovec) via isolated limb infusion (ILI) administration in approximately 6 participants with LGMD2D.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Limb-Girdle Muscular Dystrophy, Type 2D
Keywords
limb girdle muscular dystrophy, LGMD2D, alpha-sarcoglycan, gene transfer, adeno-associated virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion)
Arm Type
Experimental
Arm Description
Non-ambulant participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to a single limb on Day 0.
Arm Title
Cohort 1B Low Dose (Bilateral Limb Perfusion)
Arm Type
Experimental
Arm Description
Participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to both limbs on Day 0.
Arm Title
Cohort 2 High Dose (Bilateral Limb Perfusion)
Arm Type
Experimental
Arm Description
Participants with LGMD2D will receive 1 high dose of SRP-9004 via ILI to both limbs on Day 0.
Intervention Type
Genetic
Intervention Name(s)
SRP-9004
Other Intervention Name(s)
patidistrogene bexoparvovec
Intervention Description
Isolated Limb Infusion (ILI)
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs).
Description
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug related. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Treatment-related Treatment Emergent Adverse Event (TEAE) is defined as an TEAE that was classified by the investigator as related to treatment.
Time Frame
Up to 2 Years
Secondary Outcome Measure Information:
Title
Change From Baseline of the Distance Walked in 6 Minutes (6MWT)
Description
The 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course in 6 minutes (timed), and the distance walked (in meters) was recorded.
Time Frame
Baseline, Up to 2 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Cohort 1A must be adult and wheelchair-dependent; Cohorts 1B and 2 will be participants of age 7 or older.
Confirmed alpha-sarcoglycan deficiency or identified sarcoglycan alpha (SGCA) deoxyribonucleic acid (DNA) mutation.
Participants enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (that is, a Gowers' sign, use a handrail for climbing stairs) and walk ≤80% of predicted distance on the 6 minute walk test (6MWT) based on normative data.
Key Exclusion Criteria:
Active viral infection based on clinical observations.
The presence of SGCA mutations without weakness or loss of function.
Symptoms or signs of cardiomyopathy.
Serological evidence of human immunodeficiency virus (HIV), Hepatitis B, or C infection.
Diagnosis of (or ongoing treatment for) an autoimmune disease.
Participants with AAVrh74 or AAV8 binding antibody titers ≥ 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) immunoassay.
Other inclusion/exclusion criteria apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
30838895
Citation
Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR. Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion. Hum Gene Ther. 2019 Jul;30(7):794-801. doi: 10.1089/hum.2019.006. Epub 2019 Apr 19.
Results Reference
background
PubMed Identifier
21031578
Citation
Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol. 2010 Nov;68(5):629-38. doi: 10.1002/ana.22251.
Results Reference
background
PubMed Identifier
19798725
Citation
Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol. 2009 Sep;66(3):290-7. doi: 10.1002/ana.21732.
Results Reference
background
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A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D)
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