12-Month Safety and Efficacy Results from the SCiStar Study â A Phase 1/2a Trial of Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells (AST-OPC1) in Patients with Subacute Cervical Spinal Cord Injury
1Wirth III E, 2Fessler R, 3Leslie D, 4Steinberg G, 5McKenna S, 6Liu C, 7Kurpad S, 1Chen S, 1Lebkowski J
1Asterias Biotherapeutics, Fremont, CA, United states; 2Rush University, Chicago, IL, United states; 3Shepherd Center, Atlanta, GA, United states; 4Stanford University, Stanford, CA, United states; 5Santa Clara Valley Medical Center, San Jose, CA, United states; 6USC Keck Medical Center, Los Angeles, CA, United states; 7Medical College of Wisconsin, Milwaukee, WI, United states
Objective: After extensive testing for safety and efficacy in animal models of SCI, the initial clinical safety of AST-OPC1 was evaluated in a Phase 1 trial that enrolled 5 patients with neurologically complete T3-T11 SCI. Based on favorable 5-year safety data in that study, a Phase 1/2a clinical trial is underway to evaluate the safety and efficacy of AST-OPC1 in subjects with motor complete (AIS-A or AIS-B) C4-C7 cervical SCI. Recently the 12 month outcome data became available for the second cohort, which enrolled subjects who were AIS-A and who received 10 million AST-OPC1 cells.
Design/Methods: The SCiStar study is an open-label, single-arm trial evaluating three escalating doses of AST-OPC1 (2, 10, & 20 million cells) administered to five cohorts of subjects via direct intraparenchymal injection between 21 and 42 days post-SCI. Subjects are followed by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) neurological exam and other assessments including serial MRI scans to determine safety and activity of the grafts. Subjects are being followed for 1 year under the main study protocol and then followed for an additional 14 years under a long-term follow up protocol.
Results: A total of 24 subjects across the five cohorts have been dosed to date. All subjects in Cohort 1 (N=3 AIS-A subjects, 2 million cells) have completed 2 years of follow up and all subjects in Cohort 2 (N=6 AIS-A subjects, 10 million cells) have recently completed 1 year of follow up. To date, there have been no intraoperative complications and no safety issues associated with the administration of AST-OPC1. Importantly, no subject has demonstrated decreased neurological function or an ascending neurological level after administration of AST-OPC1. The have also been no serious adverse events (SAEs) related to AST-OPC1.
At 1 year of follow up, subjects in Cohort 1 had gained 1 motor level relative to baseline on either one side (1 of 3) or both sides (2 of 3) of the body. These gains have been maintained at 2 years of follow up. At 1 year of follow up in Cohort 2, 100% (6 of 6) subjects gained at least 1 motor level bilaterally and 67% (4 of 6) regained two motor levels on at least one side. The recovery of two motor levels in Cohort 2 has increased relative to the 6- and 9-month visits, at which 33% and 50% of subjects, respectively, had regained two motor levels. The percentage of subjects in Cohort 2 who recovered two motor levels compares favorably to the 26-29% rates in published reports of spontaneous recovery in this population and to a matched historical control group. The MRI results to date are consistent with the formation of a tissue matrix at the spinal cord injury site in all subjects in Cohorts 1 and 2, which suggests that AST-OPC1 cells have durably engrafted and contributed the prevention of cavitation at the injury site.
Conclusion: The results of the SCiStar study continue to demonstrate a strong safety profile for AST-OPC1. In addition, the efficacy data for 2 and 10 million cells at 1 year of follow up indicate a dose-dependent increase in the recovery of upper extremity motor function.
Support: California Institute for Regenerative Medicine (CIRM) Strategic Partnership Award
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