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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

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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/FiO(2) below 350 mmHg) were randomized (2:1 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/FiO(2) 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/FiO(2)) 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.
Keywords
COVID-19, Complement system, Complement 5, Systemic inflammation, ACTIVATION

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MLA
De Leeuw, Elisabeth, et al. “Efficacy and Safety of the Investigational Complement C5 Inhibitor Zilucoplan in Patients Hospitalized with COVID-19 : An Open-Label Randomized Controlled Trial.” RESPIRATORY RESEARCH, vol. 23, no. 1, 2022, doi:10.1186/s12931-022-02126-2.
APA
De Leeuw, E., Van Damme, K., Declercq, J., Bosteels, C., Maes, B., Tavernier, S., … Lambrecht, B. (2022). Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19 : an open-label randomized controlled trial. RESPIRATORY RESEARCH, 23(1). https://doi.org/10.1186/s12931-022-02126-2
Chicago author-date
De Leeuw, Elisabeth, Karel Van Damme, Jozefien Declercq, Cedric Bosteels, Bastiaan Maes, Simon Tavernier, Laurent Detalle, et al. 2022. “Efficacy and Safety of the Investigational Complement C5 Inhibitor Zilucoplan in Patients Hospitalized with COVID-19 : An Open-Label Randomized Controlled Trial.” RESPIRATORY RESEARCH 23 (1). https://doi.org/10.1186/s12931-022-02126-2.
Chicago author-date (all authors)
De Leeuw, Elisabeth, Karel Van Damme, Jozefien Declercq, Cedric Bosteels, Bastiaan Maes, Simon Tavernier, Laurent Detalle, Trevor Smart, Sophie Glatt, Nincy Debeuf, Julie Deckers, Sahine Lameire, Stefaan J. Vandecasteele, Nikolaas De Neve, Ingel K. Demedts, Elke Govaerts, Christiane Knoop, Karolien Vanhove, Michel Moutschen, Wim Terryn, Pieter Depuydt, Eva Van Braeckel, Filomeen Haerynck, Tine C. J. Hendrickx, Vanessa Parrein, Marianna Lalla, Claire Brittain, and Bart Lambrecht. 2022. “Efficacy and Safety of the Investigational Complement C5 Inhibitor Zilucoplan in Patients Hospitalized with COVID-19 : An Open-Label Randomized Controlled Trial.” RESPIRATORY RESEARCH 23 (1). doi:10.1186/s12931-022-02126-2.
Vancouver
1.
De Leeuw E, Van Damme K, Declercq J, Bosteels C, Maes B, Tavernier S, et al. Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19 : an open-label randomized controlled trial. RESPIRATORY RESEARCH. 2022;23(1).
IEEE
[1]
E. De Leeuw et al., “Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19 : an open-label randomized controlled trial,” RESPIRATORY RESEARCH, vol. 23, no. 1, 2022.
@article{8764058,
  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/FiO(2) below 350 mmHg) were randomized (2:1 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/FiO(2) 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/FiO(2)) 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.}},
  articleno    = {{202}},
  author       = {{De Leeuw, Elisabeth and Van Damme, Karel and Declercq, Jozefien and Bosteels, Cedric and Maes, Bastiaan and Tavernier, Simon and Detalle, Laurent and Smart, Trevor and Glatt, Sophie and Debeuf, Nincy and Deckers, Julie and Lameire, Sahine and Vandecasteele, Stefaan J. and De Neve, Nikolaas and Demedts, Ingel K. and Govaerts, Elke and Knoop, Christiane and Vanhove, Karolien and Moutschen, Michel and Terryn, Wim and Depuydt, Pieter and Van Braeckel, Eva and Haerynck, Filomeen and Hendrickx, Tine C. J. and Parrein, Vanessa and Lalla, Marianna and Brittain, Claire and Lambrecht, Bart}},
  issn         = {{1465-993X}},
  journal      = {{RESPIRATORY RESEARCH}},
  keywords     = {{COVID-19,Complement system,Complement 5,Systemic inflammation,ACTIVATION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{11}},
  title        = {{Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19 : an open-label randomized controlled trial}},
  url          = {{http://doi.org/10.1186/s12931-022-02126-2}},
  volume       = {{23}},
  year         = {{2022}},
}

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