Grant Award Details
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.
Grant Application Details
- 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
Therapeutic Candidate or Device
Modified adult donor bone marrow-derived mesenchymal stem cells (Modified MSC)
Chronic motor deficit secondary to ischemic stroke
Local intracerebral delivery of Modified MSC adjacent to motor pathways stimulate via a paracrine mechanism neuropoiesis & angiogenesis by the release of FGF-2, other trophic factors & ECM proteins. The net effect is alteration of synaptic transmission appearing to improve motor function in a hitherto inhibitory milieu. Collectively, these properties are thought to promote neuroplasticity seen as the basis for improvement in motor function observed in stroke patients treated with Modified MSC.
Unmet Medical Need
There are no proven medical treatments available for chronic disability secondary to stroke. Results from our Phase 1/2a study suggest that Modified MSC has a favorable safety profile and the potential to improve motor function in these patients.
Complete Ph 2b trial; EOP2 meeting; Enable Phase 3
Major Proposed Activities
- Completion of Phase 2b ACTIsSIMA clinical trial.
- Manufacture Modified MSC clinical supplies.
- Further investigate and validate the mechanisms of action to identify additional measures of potency and validation of associated bioassays.
Statement of Benefit to California:
In 2012, 96,500 Californians suffered strokes with approximately 67,500 patients experiencing residual disabilities. Results from our Phase 1/2a study suggest that Modified MSC has a favorable safety profile and the potential to improve motor function in these Californians. This research will involve many clinical & research sites throughout California which will have a positive effect on the state’s economy and scientific profile.
Source URL: https://www.cirm.ca.gov/our-progress/awards/double-blind-controlled-ph-2b-study-safety-and-efficacy-modified-stem-cells