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

Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.

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).

Keywords: 7-category ordinal scale; COVID-19; IL-6R inhibitor; Levilimab.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • COVID-19 Drug Treatment*
  • 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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT04397562