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Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease 2019 . Methods:We conducted a 24-week randomized, double-blind, placebo-controlled trial at 21 locations in the United States to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for hospitalized COVID-19 patients with elevated inflammatory markers and hypoxemia (BREATHE). Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo one week apart. The primary endpoint was all-cause mortality rate at day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge.Enrollment was halted early for futility based on an interim analysis.Results: 225 out of the planned 270 patients were randomized and dosed. 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at day 43 of 28.3% and 23.2%, respectively [adjusted difference = 5.1% versus placebo; 95% confidence interval (-6%, 17%); p = 0.377]. Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups.

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