A Phase 1 interventional study of rAAVrh74.MHCK7.DYSF.DV in Dysferlinopathy, sponsored by Sarepta Therapeutics, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-05-13.
Sponsored by Sarepta Therapeutics, Inc. · Phase 1, Interventional, and Treatment
The proposed clinical trial is a double-blind, randomized controlled study with direct intramuscular injection of rAAVrh.74.MHCK7.DYSF.DV gene vector to the extensor digitorum brevis muscle (EDB). Two cohorts of subjects with dysferlin deficiency, each with proven mutations will undergo gene transfer. A minimum of three subjects will be enrolled into each cohort.
This is a phase I safety and tolerability study with a direct intramuscular injection of rAAVrh.74.MHCK7.DYSF.DV transferred to the extensor digitorum brevis muscle (EDB). The study is designed as a randomized, controlled, dose escalation trial with one EDB receiving the rAAVrh.74.MHCK7.DYSF.DV and the other side receiving saline alone. It will follow the previously safe and effective IM gene transfer to EDB for LGMD2D.2, 3 The first cohort, inclusive of three Dysferlinopathy subjects, will receive a gene transfer total dose of 2 x 10\^12 vector genomes. Muscle biopsies will be performed at Day 45 (two subjects) and Day 90 (one subject). If there are no safety concerns, three additional subjects will be enrolled and receive an escalated dose at 6 X 10\^12 vg (total dose). Muscle biopsies in the second cohort will be performed at Day 90 (one subject) and Day 180 (two subjects). This protocol design gives us a maximum period of observation ranging from 6 weeks to 6 months to capture both transient and delayed gene expression, and to recognize sustained expression.
Sarepta Therapeutics, Inc. is the lead sponsor of 52 studies on the registry; 8 are open to participants now.
Of its 20 completed or terminated interventional studies of FDA-regulated products, 12 (60%) have results posted.
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Exclusion Criteria:
Three (n=3) dysferlin deficiency subjects will receive bilateral injections with one extensor digitorum brevis muscle (EDB) receiving the rAAVrh74.MHCK7.DYSF.DV and the other side receiving saline alone.Subjects will receive a total dose of 2 x 10\^12 in one muscle. Intervention Drug: rAAVrh.MHCK7.DYSF.DV
Drug: rAAVrh74.MHCK7.DYSF.DV
Three (n=3) dysferlin deficiency subjects will receive bilateral injections with one extensor digitorum brevis muscle (EDB) receiving the rAAVrh74.MHCK7.DYSF.DV and the other side receiving saline alone.Subjects will receive a total dose of 6 x 10\^12 vg in one muscle. Intervention Drug: rAAVrh74.MHCK7.DYSF.DV
Drug: rAAVrh74.MHCK7.DYSF.DV
Biological/Vaccine: rAAVrh74.MHCK7.DYSF.DV Recombinant adeno-associated virus carrying a dysferlin transgene under control of a muscle specific MHCK7 promoter.
Determination of safety based on the development of unacceptable toxicity
Defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity
Time frame: 2 Years
Number of participants showing dysferlin protein expression in muscle tissue
More than 3 fold increase in dysferlin protein expression in muscle compared to control side by western blot or more than 30% increase in dysferlin-expressing fibers Dysferlin protein expression as demonstrated with N -terminal anti-dysferlin antibodies will be quantified using BioQuant
Time frame: 2 Years
Leukocyte marker counts including CD45, CD3, CD4, CD8, and MAC 387.
Number of CD4+ cells/ mm2 area; Number of CD8+ cells/ mm2 area; Number of muscle fibers expressing MHCI staining / mm2 area; Number of muscle fibers expressing MHCII staining / mm2 area
Time frame: 2 Years
Binding antibodies counts and ELISpot counts to both rAAVrh74 capsid and dysferlin protein.
AAVrh74 or AAV8 binding antibody titers \> 1:50 as determined by ELISA immunoassay
Time frame: 2 Years
Number of inflammatory cells in muscle
Number of inflammatory cells per mm2 area
Time frame: 2 Years
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
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Sarepta Therapeutics, Inc.