Introduction: B01-02 was a double-blind, placebo-controlled study of ischemic stroke patients (NIHSS 8-20, inclusive) treated within 24-48 hours of symptom onset with MultiStem, an adult, adherent, stem cell product. In pre-clinical models of stroke, MultiStem appears to confer improved neurological benefit through multiple mechanisms, including down-regulation of the peripheral immune response. We sought to determine whether this observation translated to acute ischemic stroke patients treated with MultiStem.
Methods: Patients were randomized 1:1 and received IV infusion of 1.2 billion cells or placebo. After randomization, patients had blood drawn to determine baseline levels of circulating levels of CD3+ cells or specific inflammatory cytokines. Blood was drawn again at days 2, 7 and 30 post-treatment to determine the average fold change from baseline in each patient at each time point.
Results: 126 patients formed the Intention-To-Treat (ITT) population, 65 receiving MultiStem, 61 placebo. 38 MultiStem patients and 40 placebo patient samples were analyzed for CD3+ cells, while 60 MultiStem patients and 55 placebo patients samples were analyzed for serum cytokine levels. CD3+ cell levels were significantly decreased in the MultiStem treatment group compared to placebo (p=0.001) at Day 2, but not later. IL-6 (p=.031) and IL-12 (p=.035) were both significantly downregulated in the MultiStem treatment group at Day 7. IL-1β (p=.065), TNF-α (p=.068) and IFN-γ (p=.100) also trended towards being significantly reduced at Day 7.
Conclusions: IV administration of MultiStem within 24-48 hours of an ischemic stroke results in decreased circulating CD3+ cells, while reducing inflammatory cytokines in the blood during the first 7 days after onset of symptoms. These results support the hypothesis that MultiStem treatment limits the activation of the innate immune system’s response to stroke, which may provide improved neurological and recovery outcomes. Additional studies are required to confirm this observation and optimize the time of administration for MultiStem mediated benefit