Objective and design The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. Subjects The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. Treatment 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. Methods The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. Results 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 ( P = .0017). The frequency of adverse drug reactions was comparable between the groups. Conclusion In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. Trail registration The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).
【저자키워드】 COVID-19, Levilimab, IL-6R inhibitor, 7-category ordinal scale, 【초록키워드】 Efficacy, Severe COVID-19 pneumonia, COVID-19 pneumonia, clinical trial, therapy, Hospitalized, Trial, Open-label, severe COVID-19, IL-6, Infection, Ventilation, oxygen, Symptoms, Randomized, Deterioration, non-responders, Patient, Oxygen therapy, Clinical improvement, Efficacy and safety, Placebo, women, SARS-CoV-2 pneumonia, inhibitor, patients, placebo-controlled, Ordinal Scale, Adverse drug reaction, Combination, Adverse drug reactions, administration, Frequency, 7-category ordinal scale, double-blind, IL-6 receptor, subcutaneous administration, Standard of care, Older, Missing data, subject, efficacy analysis, all subjects, Registered, investigator, primary efficacy endpoint, responders, men, objective, Result, evaluate, proportion, Day, comparable, groups, sustained, receive, 1:1, all subject, eligible, 【제목키워드】 Randomized, Efficacy and safety, multicenter, placebo-controlled, clinical study, COVID-19 patient, double-blind,