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 Article

Full Text via DOI: 10.1046671016/j.ebiom.2023.104667 Web of Science: 001043942700001

Cited authors

  • Mabrey FL, Nian H, Yu C, Barnes EM, Malhotra U, Mikacenic C, Goldstein J, Mahony SO', Garcia-Diaz J, Finn P, Voelker K, Morrell ED, Self WH, Becker PM, Martin TR, Wurfel MM

Abstract

  • 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 COVID19 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-torecovery 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-1 beta and TNF-alpha. 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.

Authors

Publication date

  • 2023

International Standard Serial Number (ISSN)

  • 2352-3964

Number of pages

  • 12

Volume

  • 93