Journal Article

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

Lomakin, Nikita V., Popov, Vladimir V., Bakirov, Bulat A., Zinkina-Orikhan, Arina V., Morozova, Maria A., Mazurov, Vadim I., Linkova, Yulia N., Moiseeva, Olga M., Fomina, Darya S., Pasechnik, Elena S., Musaev, Gaziyavdibir H., Seleznev, Anton I., Lutckii, Anton A., Smolyarchuk, Elena A., Gordeev, Ivan G., Eremeeva, Anna V., Dokukina, Ekaterina A., Protsenko, Denis N., Gilyarov, Mikhail Yu, Pukhtinskaia, Polina S.

2021

Overview

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).

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adolescent / Adult / Aged / Aged, 80 and over / Allergology / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Biomedical and Life Sciences / Biomedicine / Clinical trials / Coronaviruses / COVID-19 / COVID-19 Drug Treatment / Dermatology / Double-Blind Method / Double-blind studies / Endpoint Determination / Female / Humans / Immunology / Injections, Subcutaneous / Interleukin 6 / Interleukin 6 receptors / Male / Mechanical ventilation / Middle Aged / Missing data / NCT / NCT04397562 / Neurology / Original / Original Research Article / Oxygen Inhalation Therapy / Patients / Pharmacology/Toxicology / Placebos / Pneumonia / Receptors, Interleukin-6 - antagonists & inhibitors / Respiration, Artificial / Rheumatology / Safety / Severe acute respiratory syndrome coronavirus 2 / Side effects / Therapy / Treatment Outcome / Ventilation / Viral diseases / Young Adult