Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage.

Autor: Avadhani R; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA., Ziai WC; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA.; Division of Neurocritical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Thompson RE; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Mould WA; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA., Lane K; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA., Nanni A; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA., Iacobelli M; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA., Sharrock MF; Division of Neurocritical Care, Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sansing LH; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA., Van Eldik LJ; Sanders-Brown Center on Aging and Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Hanley DF; BIOS Clinical Trials Coordinating Center, Johns Hopkins School of Medicine, 750 East Pratt Street, 16th Floor, Baltimore, MD, 21202, USA. dhanley@jhmi.edu.
Jazyk: angličtina
Zdroj: Neurocritical care [Neurocrit Care] 2024 Apr; Vol. 40 (2), pp. 807-815. Date of Electronic Publication: 2023 Nov 02.
DOI: 10.1007/s12028-023-01867-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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