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.
washington; swedish; covid-19
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.
Critical Care Medicine
Mabrey, F Linzee; Nian, Hui; Yu, Chang; Barnes, Elizabeth M; Malhotra, Uma; Mikacenic, Carmen; Goldstein, Julia; O'Mahony, D Shane; Garcia-Diaz, Julia; Finn, Patricia; Voelker, Kirk; Morrell, Eric D; Self, Wesley H; Becker, Patrice M; Martin, Thomas R; and Wurfel, Mark M, "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." (2023). Articles, Abstracts, and Reports. 7465.