Patients with acute spontaneous
intracerebral hemorrhage (ICH) develop secondary
neuroinflammation and
cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of
acute brain injury have shown that a novel small-molecule
drug candidate,
MW01-6-189WH (
MW189), decreases
neuroinflammation and
cerebral edema and improves functional outcomes.
MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a
Biomarker and
Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of
MW189 in patients with acute ICH, identify trends in potential mitigation of
neuroinflammation and
cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous
MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a "worst-case" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal
edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of
MW189, and inflammatory
cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting
neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.