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Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial.
De Leeuw, Elisabeth; Van Damme, Karel F A; Declercq, Jozefien; Bosteels, Cedric; Maes, Bastiaan; Tavernier, Simon J; Detalle, Laurent; Smart, Trevor; Glatt, Sophie; Debeuf, Nincy; Deckers, Julie; Lameire, Sahine; Vandecasteele, Stefaan J; De Neve, Nikolaas; Demedts, Ingel K; Govaerts, Elke; Knoop, Christiane; Vanhove, Karolien; Moutschen, Michel; Terryn, Wim; Depuydt, Pieter; Van Braeckel, Eva; Haerynck, Filomeen; Hendrickx, Tine C J; Parrein, Vanessa; Lalla, Marianna; Brittain, Claire; Lambrecht, Bart N.
  • De Leeuw E; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Van Damme KFA; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Declercq J; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Bosteels C; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Maes B; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Tavernier SJ; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Detalle L; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Smart T; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Glatt S; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Debeuf N; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Deckers J; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Lameire S; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Vandecasteele SJ; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • De Neve N; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Demedts IK; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Govaerts E; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Knoop C; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Vanhove K; Primary Immunodeficiency Research Lab, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Moutschen M; UCB Biopharma SRL, Braine-l'Alleud, Belgium.
  • Terryn W; UCB Pharma, Slough, UK.
  • Depuydt P; UCB Pharma, Slough, UK.
  • Van Braeckel E; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Haerynck F; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Hendrickx TCJ; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Parrein V; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Lalla M; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
  • Brittain C; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Lambrecht BN; Department of Infectious Diseases, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium.
Respir Res ; 23(1): 202, 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-2214585
ABSTRACT

BACKGROUND:

The efficacy and safety of complement inhibition in COVID-19 patients is unclear.

METHODS:

A multicenter randomized controlled, open-label trial. Hospitalized COVID-19 patients with signs of systemic inflammation and hypoxemia (PaO2/FiO2 below 350 mmHg) were randomized (21 ratio) to receive standard of care with or without the C5 inhibitor zilucoplan daily for 14 days, under antibiotic prophylaxis. The primary outcome was improvement in oxygenation at day 6 and 15.

RESULTS:

81 patients were randomly assigned to zilucoplan (n = 55) or the control group (n = 26). 78 patients were included in the safety and primary analysis. Most were men (87%) and the median age was 63 years. The mean improvement in PaO2/FiO2 from baseline to day 6 was 56.4 mmHg in the zilucoplan group and 20.6 mmHg in the control group (mean difference + 35.8; 95% confidence interval (CI) - 9.4 to 80.9; p = 0.12), an effect also observed at day 15. Day 28 mortality was 9% in the zilucoplan and 21% in the control group (odds ratio 0.4; 95% CI 0.1 to 1.5). At long-term follow up, the distance walked in a 6-min test was 539.7 m in zilucoplan and 490.6 m in the control group (p = 0.18). Zilucoplan lowered serum C5b-9 (p < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified.

CONCLUSION:

Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO2/FiO2) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment / Anti-Infective Agents Type of study: Cohort study / Experimental Studies / Prognostic study / Randomized controlled trials Limits: Female / Humans / Male / Middle aged Language: English Journal: Respir Res Year: 2022 Document Type: Article Affiliation country: S12931-022-02126-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment / Anti-Infective Agents Type of study: Cohort study / Experimental Studies / Prognostic study / Randomized controlled trials Limits: Female / Humans / Male / Middle aged Language: English Journal: Respir Res Year: 2022 Document Type: Article Affiliation country: S12931-022-02126-2