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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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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
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author 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
author_facet 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
author_sort Kurth, Florian
collection PubMed
description 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.
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spelling pubmed-97806362022-12-23 Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial 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 J Glob Antimicrob Resist Short Communication 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. The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. 2023-03 2022-12-23 /pmc/articles/PMC9780636/ /pubmed/36572146 http://dx.doi.org/10.1016/j.jgar.2022.12.004 Text en © 2022 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Short Communication
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
Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial
title Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial
title_full Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial
title_fullStr Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial
title_full_unstemmed Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial
title_short Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial
title_sort cenicriviroc for the treatment of covid-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase ii trial
topic Short Communication
url 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
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