Authors: David O. Okonkwo, MD, PhD, FAANS; Peter McAllister, MD; Masahito Kawabori, MD, PhD; Jefferson Chen, MD, PhD; Benjamin Frishberg, MD; Achal Achrol, MD; Robert Gross, MD, PhD; Gary Steinberg, MD, PhD; Hideaki Imai, MD; Daniel Lu, MD, PhD; Takao Yasuhara, MD; Damien Bates, MD, PhD (Pittsburgh, PA)
Introduction: Traumatic brain injury (TBI) is a major cause of permanent motor and cognitive impairment for which no effective treatments are available. Methods: This 6-month pre-specified interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of allogeneic modified bone marrow-derived mesenchymal stem cells (SB623) in patients with stable chronic motor deficits secondary to TBI. This international trial enrolled 61 subjects (mean age 34 years) from 18 sites in the US, Japan, and Ukraine. Subjects underwent stratified randomization using baseline GOS-E score to assign in a 1:1:1:1 ratio to either 2.5x10 6 , 5.0x10 6 , 10x10 6 SB623 cells or surgical sham procedure. Safety was assessed in all enrolled subjects. Efficacy analyses were conducted on the modified intent-to-treat population of randomized subjects completing surgery (N=61; SB623=46, sham controls=15). Primary efficacy outcome was mean change from baseline in the Fugl-Meyer Motor Scale score (FMMS) of SB623-treated subjects compared to controls at 24 weeks. Results: Significant improvement (LS mean [SE]) from baseline motor function was observed in FMMS at Week 24 (8.7 [1.5] for SB623 versus 2.4 [2.7] in control group; P =0.04). There was no difference in rate of treatment-emergent adverse events (TEAEs) comparing SB623-treated subjects versus controls ( P =0.25), and no dose-limiting toxicities or deaths. Eight (17.4%) serious adverse events (SAEs) in five (10.9%) SB623-treated subjects occurred versus three (20%) SAEs in three (20%) controls. 92.3% of TEAEs were not likely or unlikely to be related to SB623 or control treatment, whereas 39.5% (SB623-treated) and 36.9% (control) of TEAEs were possibly, probably, or definitely related to surgical procedure. Conclusion: SB623 cell implantation was safe and well tolerated, with no significant difference in adverse events between SB623 treatment and surgical sham controls. SB623 treatment was associated with improvement in motor function at 6 months.