Anti-CD14 treatment in patients with severe COVID-19: Clinical and biological effects in a Phase 2 randomized open-label adaptive platform clinical trial
Abstract
Background and Research Question: CD14-dependent innate immunity contributes to poor outcomes in COVID-19 pneumonia. We tested the clinical and biological efficacy of a blocking monoclonal antibody to CD14 (IC14) for treatment of severe COVID-19 pneumonia and the utility of a biomarker of CD14 pathway activation in predicting outcome. Study Design and Methods: We report a preplanned secondary analysis of the I-SPY COVID Trial, which enrolled hospitalized patients with severe COVID-19 pneumonia at 19 medical centers in the U.S. who required high-level respiratory support. Participants were randomized to receive either intravenous IC14 (4 mg/kg on Day 1, then 2 mg/kg on Days 2–4) (N=67) or standard care (N=76). Primary endpoints included time-to-recovery, defined as the first two-day period on ≤6L/min O2, and mortality. In predefined secondary analyses, we tested the association between IC14 treatment and mortality in patients with high or low baseline plasma presepsin (sCD14-ST), a biomarker of CD14 pathway activity, and the effects of IC14 on plasma biomarkers of pharmacodynamics, injury and inflammation. Results: IC14 treatment did not improve time-to-recovery or 28-day mortality in the overall population, and the trial was stopped due to meeting futility criteria for the time-to-recovery endpoint. However, a predefined sub-group analysis showed that IC14 treatment was associated with a numerical reduction in 28-day mortality in participants with high (above median)…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 76 participants or records.
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