Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial.

Abstract

We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted.

• Authors: Endry H T Lim, Alexander P J Vlaar, Lieuwe D J Bos, Lonneke A van Vught, Anita M Tuip-de Boer, Romein W G Dujardin, Maria Habel, Zhongli Xu, Matthijs C Brouwer, Diederik van de Beek, Sanne de Bruin, Amsterdam UMC COVID-19 Biobank Investigators
• Journal: Respiratory research (Respir Res) Vol. 23 Issue 1 Pg. 375 (Dec 24 2022) ISSN: 1465-993X [Electronic] England
• PMID: 36566174 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase II, Letter)
• Copyright: © 2022. The Author(s).

Chemical References

• vilobelimab
• Complement C5a
• Biomarkers

Topics

• Humans
• COVID-19
• SARS-CoV-2
• Complement C5a
• Inflammation (diagnosis, drug therapy)
• Biomarkers