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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
2023
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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. |
format | Online Article Text |
id | pubmed-9780636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. |
record_format | MEDLINE/PubMed |
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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