Abstract TP20: Intravenous Glibenclamide For Large Hemispheric Infarction: Baseline Data From Initial Enrollees In The Charm Phase 3 Study

Abstract

Objective: To present baseline data from initially enrolled participants in CHARM, a Phase 3 study evaluating whether intravenous (IV) glibenclamide (BIIB093) improves functional outcomes at 90 days in individuals with large hemispheric infarction (LHI) compared with placebo. Background: In preclinical models, glibenclamide reduces cerebral edema due to LHI by inhibiting the SUR1/TRPM4 cation channel. Phase 2 trial data suggested that glibenclamide compared with placebo may reduce 30-day mortality and increase rates of favorable functional outcomes. Design/Methods: CHARM is a global, randomized, double-blind, placebo-controlled trial (NCT02864953). Eligible participants (planned enrollment: 768) are 18-85 years old, with a diagnosis of acute ischemic stroke of the middle cerebral artery territory, and study drug treatment initiated within 10 hours of last known normal (LKN) time. Randomization is (1:1) to a 72-hour continuous infusion of glibenclamide or placebo and may receive standard of care reperfusion therapy. The primary endpoint is ordinal analysis of the modified Rankin Scale at 90 days in participants ≤70 years of age. Results: As of January 2021, 264 participants were randomized and 249 were dosed. Mean (SD) age 64 (12.4) years (n=249). Median time from LKN to dosing was 9.3 hours. At baseline, mean (SD) National Institute of Health Stroke Scale score was 20.4 (5.09); IQR (17-23). Participants with baseline imaging data (n=259) had documented qualifying LHI on MRI (38.6%), computed tomography perfusion (CTP; 35.1%), or non-contrast computed tomography (26.3%). Site investigator-read median infarct size on MRI/CTP was 135 mL (IQR 99 - 174 mL, n=249). Conclusions: Initially enrolled CHARM participants have imaging evidence of LHI and moderate-to-severe neurologic deficits. Ages 71-85 years have completed enrollment; remaining enrollees in CHARM will be ≤70 years of age. Enrollment is ongoing.