Intracranial implantation of SB623 cells was safe and well tolerated in patients with chronic TBI, and was associated with statistically significant improvement in motor status at 24 weeks.
Objective : To determine if intracranial implantation of SB623 cells can improve chronic motor deficits secondary to traumatic brain injury (TBI).
Design : A Phase 2, randomized, double-blind, surgical sham-controlled study (NCT02416492). Pre-specified 24-week interim analysis results are reported.
Setting : Patients were enrolled at 18 hospital centers in the US, Japan, and Ukraine.
Participants (or Animals, Specimens, Cadavers) : 61 patients (SB623=46, sham controls=15) with stable chronic motor deficits secondary to TBI.
Interventions : Allogeneic modified bone marrow-derived mesenchymal stem cells (SB623) were implanted via stereotactic intracranial injection. Patients were randomly stratified using a 1:1:1:1 ratio (2.5x106, 5.0x106, 10x106 SB623 cells, or surgical sham).
Main Outcome Measure(s) : Fugl-Meyer Motor Scale score (FMMS) change from baseline to 24 weeks, comparing SB623-treated patients versus controls.
Results : Treatment with SB623 cells was safe, with no dose-limiting toxicities or deaths. There was no significant difference in rate of treatment-emergent adverse events between groups (P=0.25). Serious adverse events were seen in five (10.9%) SB623-treated patients (two pre-operatively) versus three (20%) controls. In the modified intent-to-treat population of randomized patients completing surgery (N=61), FMMS score change from baseline to Week 24 was significantly greater for the combined SB623 group (n=46) compared to controls (n=15) (8.7±1.5 versus 2.4±2.7 points, P=0.04, least square mean±SE). The 5.0x106 SB623 group (n=15) experienced greatest FMMS score improvement at Week 24 (11.9±2.3 points), also significantly greater than controls (P=0.006). Significantly more SB623-treated patients than controls achieved the FMMS clinically meaningful threshold change of ≥10 points at Week 24 (39.1% versus 6.7%, P=0.04), a threshold that was achieved by 53.3% of the 5.0x106 SB623 group (P=0.015 versus control).
Conclusions : Intracranial implantation of SB623 was safe and well tolerated in patients with chronic TBI, and was associated with statistically significant improvement in motor status at 24 weeks.