Clinical trial NCT01976091: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Limb-Girdle Muscular Dystrophy, Type 2D
Keywords: limb girdle muscular dystrophy
LGMD2D
alpha-sarcoglycan
gene transfer
adeno-associated virus
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nationwide Children's Hospital
First posted: 2013-11-05
Enrollment: 6
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs).
timeFrame: Up to 2 Years
Secondary outcomes:
measure: Change From Baseline of the Distance Walked in 6 Minutes (6MWT)
timeFrame: Baseline, Up to 2 Years
Other outcomes:
Locations:
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
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.
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.
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.