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.

Abstract

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).

• Authors: 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
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 70 Issue 10-12 Pg. 1233-1246 (Dec 2021) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 34586459 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Monoclonal, Humanized
• Receptors, Interleukin-6
• levilimab

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Double-Blind Method
• Endpoint Determination
• Female
• Humans
• Injections, Subcutaneous
• Male
• Middle Aged
• Oxygen Inhalation Therapy
• Receptors, Interleukin-6 (antagonists & inhibitors)
• Respiration, Artificial
• Treatment Outcome
• Young Adult
• COVID-19 Drug Treatment