Introduction: MultiStem is an adult, adherent, stem cell product, having shown safety and efficacy in other clinical indications and pre-clinical models of stroke. We assessed whether it was safe and improved outcomes in patients with ischemic stroke.
Methods: B01-02 was a double-blind, placebo-controlled study of ischemic stroke patients (NIHSS 8-20, inclusive) treated within 24-48 hours of symptoms at 33 sites in the U.S. and U.K. Patients were randomized 1:1 and received infusion of 1.2 billion cells or placebo. Efficacy endpoints included Global Recovery (mRS ≤2, NIHSS Δ ≥75% and BI ≥95) and Excellent Outcome between groups (mRS ≤1, NIHSS ≤1, BI ≥95) at Day 90, among others. Safety end points included neurologic worsening, secondary infections, adverse events and mortality.
Results: 126 patients formed the Intention-To-Treat (ITT) population, 65 receiving MultiStem, 61 placebo. The cell therapy did not show a significant benefit relative to placebo for the primary and secondary endpoints. However, MultiStem treatment was associated with lower rates of infections and pulmonary events, a reduction in hospitalization, and a reduction in life threatening adverse events and death. A higher proportion of patients receiving MultiStem treatment achieved an Excellent Outcome (p=0.10) compared to placebo. Post-hoc analyses indicate that, compared to placebo subjects (n=52), patients who received cell treatment earlier in the treatment window (≤36 hrs, n=27) had better Global Recovery (41.9% vs. 17.3%, p<0.01) and Excellent Outcome (18.5% v. 3.8%, p=0.03), had significantly better recovery by mRS shift analysis (p=0.03) and significantly reduced hospitalization (6.7d vs. 10.3 d, p<0.01).
Conclusions: Administration of MultiStem is safe and well tolerated in ischemic stroke patients within 48 hours of onset and reduces adverse events and death. Post-hoc analyses suggest that earlier administration of MultiStem may provide therapeutic benefit. Additional clinical studies exploring the optimal time frame for MultiStem administration are warranted.