Background / Objective: 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. PATIENTS AND 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 days 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 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 baseline, respectively). In the mITT 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 (ARDS), the remaining had a favourable outcome. Treatment with CVC was overall well tolerated, with most adverse events (AEs) being grade I or II and resolving spontaneously. CONCLUSION: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy.
- Kurth, F.
- Helbig, E. T.
- Lippert, L. J.
- Thibeault, C.
- Barbone, G.
- Eckart, M. A.
- Kluge, M.
- Puengel, T.
- Demir, M.
- Röhle, R.
- Keller, T.
- Ruwwe-Glösenkamp, C.
- Witzenrath, M.
- Suttorp, N.
- von Kalle, C.
- Sander, L. E.
- Jochum, C.
- Tacke, F.
Keywords
- Ards
- Covid-19
- Cenicriviroc
- SARS-CoV-2
- clinical trial
