Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia.

Autor:	Mabrey FL; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA., Nian H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Yu C; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Barnes EM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA., Malhotra U; Benaroya Research Institute at Virginia Mason, Seattle, WA, USA; Virginia Mason Franciscan Health, Seattle, WA, USA., Mikacenic C; Benaroya Research Institute at Virginia Mason, Seattle, WA, USA; Virginia Mason Franciscan Health, Seattle, WA, USA., Goldstein J; National Institute of Allergy and Infectious Diseases, National Institute of Health, USA., O'Mahony DS; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USA., Garcia-Diaz J; Ochsner Medical Center, New Orleans, LA, USA., Finn P; University of Illinois Hospital and Health Sciences System, University of Illinois College of Medicine, Chicago, IL, USA., Voelker K; Sarasota Memorial Healthcare System, Sarasota, FL, USA., Morrell ED; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA., Self WH; Vanderbilt Institute for Clinical and Translational Research and Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Becker PM; National Institute of Allergy and Infectious Diseases, National Institute of Health, USA., Martin TR; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA., Wurfel MM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: mwurfel@uw.edu.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2023 Jul; Vol. 93, pp. 104667. Date of Electronic Publication: 2023 Jun 17.
DOI:	10.1016/j.ebiom.2023.104667
Abstrakt:	Background: Severe COVID-19 is associated with innate immunopathology, and CD14, a proximal activator of innate immunity, has been suggested as a potential therapeutic target. Methods: We conducted the COVID-19 anti-CD14 Treatment Trial (CaTT), a Phase II randomized, double-blind, placebo-controlled trial at 5 US-sites between April 12, 2021 and November 30, 2021 (NCT04391309). Hospitalized adults with COVID-19 requiring supplemental oxygen (<30 LPM) were randomized 1:1 to receive 4 daily doses of intravenous IC14, an anti-CD14 monoclonal antibody, or placebo. All participants received remdesivir. The primary outcome was time-to-resolution of illness, defined as improvement on the 8-point NIH-Ordinal COVID-19 Scale to category ≤3. Secondary endpoints were safety and exploratory endpoints were pro-inflammatory and antiviral mediators in serum on days 0-5 & 7. The trial was stopped after 40 patients were randomized and treated due to slow enrollment. Findings: 40 participants were randomized and treated with IC14 (n = 20) or placebo (n = 20). The median time-to-recovery was 6 days (95% CI, 5-11) in the IC14 group vs. 5 days (95% CI, 4-10) in the Placebo group (recovery rate ratio: 0.77 (95% CI, 0.40, 1.48) (log-rank p = 0.435). The number of adverse events was similar in each group, and no IC14-attributable secondary infections occurred. In repeated-measures mixed-effects analyses, IC14 treatment increased serum sCD14 concentrations, an expected pharmacodynamic effect. Pre-planned, exploratory analyses suggested that IC14 treatment decreased the trajectories of circulating MIP-1β and TNF-α. Interpretation: IC14 treatment did not improve time-to-resolution of illness in hypoxemic patients with COVID-19 in this small trial. Results of exploratory analyses suggested IC14 had biologic effects that warrant future clinical investigation. Funding: National Institute of Allergy and Infectious Diseases. Competing Interests: Declaration of interests TRM reported: 1) receiving fees from Novartis Pharmaceuticals for the topic of COVID-19 related ARDS, 2) receiving fees from Quantum Leap Healthcare Collaborative as a member of the clinical safety monitoring committee for another trial in COVID, 3) providing unpaid consulting for Implicit Bioscience Ltd for use of the IC14 anti-CD14 monoclonal antibody in ARDS and COVID-19 illness. JGD reported receiving a fee from RMEI: Medical Education for the topic of severe COVID-19 management outside the submitted work. No other disclosures were reported. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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