Japan: Findings from Phase 2/3 TREASURE Randomized Clinical Trial (RCT)

Bone marrow-derived allogeneic stem cell therapy shortly after ischemic stroke was found to be safe but failed to improve short-term outcomes. The findings were published online in JAMA Neurology on January 16, 2024.

In the RCT with 206 participants, intravenous (IV) administration of intravenous allogeneic multipotent adult progenitor cell (MultiStem) therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes at 90 days compared with placebo. No grade 3 or 4 allergic reactions were observed, including in older patients.

"There was no significant difference in the rate of excellent outcomes -- a composite of a modified Rankin Scale (mRS) score of 1 or below, a NIHSS score of 1 or less, and a Barthel index score (BI) of 95 or greater -- between treatment and placebo groups (11.5% vs 9.8%; adjusted risk difference 0.5%)," the researchers reported.

However, exploratory subgroup analyses in patients with mRS scores of 0-2 at day 90 who were treated with the investigational MultiStem seemed to show better outcomes, particularly for patients with ischemic core volumes of 50 mL or more and those aged 64 or younger.

Cell therapy is touted as a promising treatment approach for stroke and other diseases. However, there is no information on whether MultiStem (HLCM051), a bone marrow–derived, allogeneic, multipotent adult progenitor cell product, holds the potential for ischemic stroke treatment. Kiyohiro Houkin, Hokkaido University, Sapporo, Japan, and colleagues aimed to assess the safety and efficacy of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.

For this purpose, 206 adults from academic and clinical centres in Japan who had an acute ischemic stroke (baseline NIHSS score of 8-20), an mRS score of 0 or 1 before stroke onset, and confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis, were included.

Patients with lacunar or brainstem infarction, those who received combined reperfusion therapy, and those with a change in NIHSS score of 4 or greater during a minimum period of 6 hours between screening and randomization were excluded.

The mean age of the participants was 76.5 years, and 54.4% were male. They received a single IV dose of allogeneic stem cell therapy or placebo for 30-60 minutes between 18 and 36 hours after stroke onset. Patient visits were scheduled at 7, 30, 90, and 365 days following randomization, with phone calls at day 60 and every 2 months after day 90.

Study Endpoints

• The primary endpoints of the study were excellent and safety outcomes at day 90, measured as a composite of a mRS score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater.
• The secondary endpoints were excellent outcomes at day 365, mRS scores of 0 to 1 and 0 to 2 at day 90, and mRS score distribution at days 90 and 365.

Findings

• The study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 years, and more than half of patients were men (54.4%).
• There were no between-group differences in primary and secondary endpoints.
• The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (11.5% versus 9.8%; adjusted risk difference, 0.5%).
• The frequency of adverse events was similar between treatment groups.

"In this randomized clinical trial, IV administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve outcomes at 90 days," the researchers wrote. However, efficacy was indicated in patients with large infarcts and possibly in younger patients based on exploratory subgroup analyses with no correction for multiple comparisons.

"To confirm the safety and efficacy of MultiStem therapy, the combined analysis of the TREASURE and ongoing MASTERS-2 trials will be conducted," they concluded.

Reference

Houkin K, Osanai T, Uchiyama S, et al. Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial. JAMA Neurol. Published online January 16, 2024. doi:10.1001/jamaneurol.2023.5200