A Double-Blind, Controlled Ph 2b Study of the Safety and Efficacy of Modified Stem Cells in Patients with Chronic Motor Deficit from Ischemic Stroke

CLINICAL TRIAL SUMMARY: SanBio conducted SB-STR02 (NCT02448641) “A Double-Blind, Controlled Phase 2B Study of the Safety and Efficacy of Modified Stem Cells (SB623) in Patients with Chronic Motor Deficit from Ischemic Stroke” from December 2015 through December 2018; SB-STR02 was partially supported by CIRM’s Award of CLIN2-10344. The study was a randomized, double-blind sham surgery controlled trial. SB623 cells were implanted in the peri-infarct region. Enrolled patients suffered from chronic stroke defined as patients > 6 months post ischemic stroke (up to 7.5 years) with persistent motor deficits that correlate with the location of the infarct (MCA territory). Patients were randomized to one of three treatment groups: 2.5 million SB623 cells, 5 million SB623 cells, and a sham surgery (control) group. The primary efficacy endpoint was the proportion of patients whose Fugl-Meyer Motor Score (FMMS) improved by ≥ 10 point change at Month 6 from Baseline. The secondary efficacy endpoints were the proportion of patients for whom: (a) Modified Rankin Scale improved by ≥ 1 point at Month 6 from Baseline, (b) Action Research Arm Test (ARAT) improved by ≥ 6 points at Month 6 from Baseline, (c) Gait Velocity on standard 10 m walk improved at least one functional level at Month 6 from Baseline, (d) mean change from Baseline in T-scores at Month 6 of Neurological Quality of Life (NeuroQOL) sub-domains: upper extremity function (fine motor ADL) and lower extremity function (mobility), and (e) Global Rating of Perceived Change scores at Month 6 were 7 (much better) or 6 (a little improved) as assessed by patient (or caregiver) and by clinician. 163 patients were treated at 58 sites (assessment and surgical), the study enrolled over two years and there were 12 months of follow-up. The SB-STR02 trial did not meet its primary endpoint as the SB623 treatment groups did not demonstrate a statistically significant improvement compared to the control group. No safety issues were observed for SB523 POTENCY ASSAY SUMMARY: Release testing of SB623 lots for clinical use has utilized the measurement of fibroblast growth factor 2 (FGF2) concentration in extracts of mesenchymal stem cells (MSC) or SB623 cells since 2015. The original method used a commercially available ELISA kit and was not optimized to a level meeting ICH Q2 (R1) validation requirements. SanBio has continued to develop an FGF2 assay through evaluation of a number of variables such as lysis buffer, dilution ratios, cell concentration and treatment time. The assay developed under this award yields reliable, reproducible results which will be further qualified and validated.