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Clinical Trial
. 2022 Dec 24;23(1):375.
doi: 10.1186/s12931-022-02278-1.

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

Endry H T Lim  1   2   3   4   5 , Alexander P J Vlaar  6   7 , Lieuwe D J Bos  6   7 , Lonneke A van Vught  6   8 , Anita M Tuip-de Boer  6   7 , Romein W G Dujardin  6   7 , Maria Habel  9 , Zhongli Xu  9 , Matthijs C Brouwer  10   11 , Diederik van de Beek  10   11 , Sanne de Bruin  6   7 ; Amsterdam UMC COVID-19 Biobank Investigators
Collaborators, Affiliations
Clinical Trial

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

Endry H T Lim et al. Respir Res. .

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.

Keywords: C5a; COVID-19; Complement; Complement inhibition; SARS-CoV-2; Vilobelimab.

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Conflict of interest statement

Prof. Dr. Vlaar reports personal fees from InflaRx paid to Amsterdam UMC, during conduct of the study. Dr. Habel and Dr. Xu are employees of InflaRx. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
C3a, C5a, factor Bb, MASP-2, thromboxane A2, ADAMTS13 and IL-8. Mean predictions of the LMMs per group are plotted in the graphs. ADAMTS13 a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, BSC best supportive care, IL-8 interleukin-8, MASP-2 Mannan-binding lectin serine protease 2
See this image and copyright information in PMC

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