The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
Nikita V Lomakin, Bulat A Bakirov, Denis N Protsenko, Vadim I Mazurov, Gaziyavdibir H Musaev, Olga M Moiseeva, Elena S Pasechnik, Vladimir V Popov, Elena A Smolyarchuk, Ivan G Gordeev, Mikhail Yu Gilyarov, Darya S Fomina, Anton I Seleznev, Yulia N Linkova, Ekaterina A Dokukina, Anna V Eremeeva, Polina S Pukhtinskaia, Maria A Morozova, Arina V Zinkina-Orikhan, Anton A Lutckii
Inflammation Research, doi:10.1007/s00011-021-01507-5
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.
Authors and Affiliations Nikita V. Lomakin
References
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DOI record:
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"abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Objective and design</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Subjects</jats:title>\n <jats:p>The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Treatment</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (<jats:italic>P </jats:italic>= .0017). The frequency of adverse drug reactions was comparable between the groups.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Trail registration</jats:title>\n <jats:p>The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).</jats:p>\n </jats:sec>",
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