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Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial

OBJECTIVES: C-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID...

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Detalles Bibliográficos
Autores principales: Kurth, Florian, Helbig, Elisa T., Lippert, Lena J., Thibeault, Charlotte, Barbone, Gianluca, Eckart, Marius A., Kluge, Martin, Puengel, Tobias, Demir, Münevver, Röhle, Robert, Keller, Theresa, Ruwwe-Glösenkamp, Christoph, Witzenrath, Martin, Suttorp, Norbert, von Kalle, Christof, Sander, Leif E., Jochum, Christoph, Tacke, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780636/
https://www.ncbi.nlm.nih.gov/pubmed/36572146
http://dx.doi.org/10.1016/j.jgar.2022.12.004
Descripción
Sumario:OBJECTIVES: C-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID-19. Here we report human data on use of a chemokine receptor inhibitor in patients with COVID-19. METHODS: Interim results of a 2:1 randomised, placebo-controlled, investigator-initiated trial on the CCR2/CCR5-inhibitor Cenicriviroc (CVC) 150 mg BID orally for 28 d in hospitalised patients with moderate to severe COVID-19 are reported. The primary endpoint is the subject's responder status defined by achieving grade 1 or 2 on the 7-point ordinal scale of clinical improvement on day 15. RESULTS: Of the 30 patients randomised, 18 were assigned to receive CVC and 12 to placebo. Efficient CCR2- and CCR5 inhibition was demonstrated through CCL2 and CCL4 elevation in CVC-treated patients (485% and 80% increase on day 3 compared to the baseline, respectively). In the modified intention-to-treat population, 82.4% of patients (14/17) in the CVC group met the primary endpoint, as did 91.7% (11/12) in the placebo group (OR = 0.5, 95% CI = 0.04–3.41). One patient treated with CVC died of progressive acute respiratory distress syndrome, and the remaining had a favourable outcome. Overall, treatment with CVC was well tolerated, with most adverse events being grade I or II and resolving spontaneously. CONCLUSIONS: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as an intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy.