The primary objectives of this trial are the following:
1. To determine the highest well-tolerated and safest single dose of MultiStem up to a maximum of 1200 million total cells in subjects with ischemic stroke and
2. To determine the efficacy of MultiStem on functional outcome in ischemic stroke subjects.
The secondary objectives of this trial are the following:
1. To determine the safety of MultiStem in subjects with ischemic stroke and
2. To determine changes in functional outcomes and disease severity outcomes of ischemic stroke subjects treated with MultiStem.
The exploratory objectives of this trial are:
1. To evaluate changes in brain imaging metrics and blood biomarker outcomes
2. To evaluate the incidence of infection (local and systemic) in ischemic stroke subjects treated with MultiStem.
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, dose-escalation trial. The total trial duration for safety and efficacy follow-up will be 12 months. Approximately 140 subjects who experienced ischemic cortical stroke and fulfill all the eligibility criteria will be enrolled into the trial in the United States and in the United Kingdom. The trial will consist of 3 treatment cohorts. In Cohort 1, 8 subjects will be randomized in a 3:1 ratio to receive an infusion of MultiStem 400 million cells (n=6) or placebo (n=2). Infusions for the first 4 subjects in Cohort 1 will be staggered by 24 hours to ensure there are no safety issues prior to dosing the next subject. Following the last subject in Cohort 1 reaching 7 days post-infusion, an Independent Safety Committee will evaluate the dose-limiting toxicity (DLT) and other safety information for the 8 subjects to determine whether it is safe to proceed to Cohort 2. In Cohort 2, 8 additional subjects will be randomized in a 3:1 ratio to receive an infusion of MultiStem 1200 million cells (n=6) or placebo (n=2). Infusions for the first 4 subjects in Cohort 2 will be staggered by 24 hours to ensure there are no safety issues prior to dosing the next subject. Once both Cohorts 1 and 2 are enrolled and the final subject is 7 days post-infusion, the Independent Safety Committee will determine the highest MultiStem dose (400 million cells or 1200 million cells) that is safe to administer to subjects in Cohort 3. In Cohort 3, approximately 120 subjects will be randomized in a 1:1 ratio (MultiStem [n=60] or placebo [n=60]) to receive an infusion of the highest well-tolerated dose of MultiStem determined from Cohorts 1 and 2. Randomization will be stratified by baseline NIHSS score (<=12 and >=13). All subjects will be enrolled continuously into Cohort 3 of the trial. Safety data from Cohort 3 will be reviewed by the Independent Safety Committee once approximately 33% and then again after approximately 66% of subjects have received investigational product and been followed through 7-day safety assessments.