Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial

Frontiers in Immunology

Immunology

Melina Stüssi-Helbling¹  Lars C. Huber¹  Marcelo R. Bacci²  Johannes Sumer³  Werner C. Albrich³  Reto Thoma³  Stephan Moser⁴  Pascal Urwyler⁴  Panteleimon Charitos⁴  Marina Leimbacher⁴  Marten Trendelenburg⁵  Michael Osthoff⁵  Ingmar A. F. M. Heijnen⁶  Parham Sendi⁷  Adrián Camacho-Ortiz⁸ 

[1] Clinic for Internal Medicine, City Hospital Triemli, Zurich, Switzerland;Department of General Practice, Centro Universitário em Saúde do ABC, Santo André, Brazil;Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland;Division of Internal Medicine, University Hospital Basel, Basel, Switzerland;Division of Internal Medicine, University Hospital Basel, Basel, Switzerland;Department of Clinical Research, University of Basel, Basel, Switzerland;Department of Biomedicine, University of Basel, Basel, Switzerland;Division of Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland;Institute for Infectious Diseases, University of Bern, Bern, Switzerland;Servicio de Infectologia, Hospital Universitario Dr. José Eleuterio González, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico;

关键词: COVID-19;    randomized trial;    C1 esterase inhibitor;    complement system;    kallikrein kinin system;    contact activation system;   

DOI  :  10.3389/fimmu.2023.1255292

 received in 2023-07-08, accepted in 2023-10-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundConestat alfa (ConA), a recombinant human C1 inhibitor, may prevent thromboinflammation.MethodsWe conducted a randomized, open-label, multi-national clinical trial in which hospitalized adults at risk for progression to severe COVID-19 were assigned in a 2:1 ratio to receive either 3 days of ConA plus standard of care (SOC) or SOC alone. Primary and secondary endpoints were day 7 disease severity on the WHO Ordinal Scale, time to clinical improvement within 14 days, and safety, respectively.ResultsThe trial was prematurely terminated because of futility after randomization of 84 patients, 56 in the ConA and 28 in the control arm. At baseline, higher WHO Ordinal Scale scores were more frequently observed in the ConA than in the control arm. On day 7, no relevant differences in the primary outcome were noted between the two arms (p = 0.11). The median time to defervescence was 3 days, and the median time to clinical improvement was 7 days in both arms (p = 0.22 and 0.56, respectively). Activation of plasma cascades and endothelial cells over time was similar in both groups. The incidence of adverse events (AEs) was higher in the intervention arm (any AE, 30% with ConA vs. 19% with SOC alone; serious AE, 27% vs. 15%; death, 11% vs. 0%). None of these were judged as being related to the study drug.ConclusionThe study results do not support the use of ConA to prevent COVID-19 progression.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT04414631.

【 授权许可】

Unknown   
Copyright © 2023 Urwyler, Leimbacher, Charitos, Moser, Heijnen, Trendelenburg, Thoma, Sumer, Camacho-Ortiz, Bacci, Huber, Stüssi-Helbling, Albrich, Sendi and Osthoff