Lenzilumab Efficacy and Safety in Newly Hospitalized COVID-19 Subjects: Results from a Phase 3 Randomized Double-Blind Placebo-Controlled Trial
Open Forum Infectious Diseases
; 8(SUPPL 1):S29, 2021.
Article
in English
| EMBASE | ID: covidwho-1746799
ABSTRACT
Background. Severe coronavirus disease 2019 (COVID-19) often results from the immune-mediated cytokine storm, triggered by granulocyte macrophage-colony stimulating factor (GM-CSF), potentially leading to respiratory failure and death. Lenzilumab, a novel anti-human GM-CSF monoclonal antibody, neutralizes GM-CSF and demonstrated potential to improve clinical outcomes in a matched case-cohort study of patients with severe COVID-19 pneumonia. This Phase 3 randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of lenzilumab to improve the likelihood of survival without invasive mechanical ventilation (SWOV), beyond available treatments. Methods. Hypoxic patients, hospitalized with COVID-19 (n=520), requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized on Day 0 to receive lenzilumab (1800mg, n=261) or placebo (n=259), and available treatments, including remdesivir and/or corticosteroids;and were followed through Day 28. Results. Baseline demographics were comparable between groups male, 64.7%;mean age, 60.5 years;median CRP, 79.0 mg/L. Patients across both groups received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the primary endpoint, likelihood of SWOV in the mITT population, by 1.54-fold (HR 1.54;95%CI 1.02-2.32, p=0.0403). Lenzilumab improved SWOV by 1.91-fold (nominal p=0.0073) and 1.92-fold (nominal p=0.0067) in patients receiving remdesivir or remdesivir and corticosteroids, respectively. A key secondary endpoint of incidence of IMV, ECMO or death was also improved in patients receiving remdesivir (p=0.020) or remdesivir and corticosteroids (p=0.0180). Treatment-emergent serious adverse events were similar across both groups. Conclusion. Lenzilumab significantly improved SWOV in hypoxic COVID-19 patients upon hospitalization, with the greatest benefit observed in patients receiving treatment with remdesivir and corticosteroids. NCT04351152.
corticosteroid; lenzilumab; oxygen; placebo; remdesivir; adult; clinical trial; cohort analysis; conference abstract; controlled study; coronavirus disease 2019; demographics; double blind procedure; drug combination; drug safety; drug therapy; hospitalization; human; incidence; invasive ventilation; major clinical study; male; middle aged; phase 3 clinical trial; randomized controlled trial; survival
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Randomized controlled trials
Language:
English
Journal:
Open Forum Infectious Diseases
Year:
2021
Document Type:
Article
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