Atibuclimab (IC14) for Treatment of Acute Decompensated Heart Failure: A Phase Ib Pilot Study.

Systemic inflammation contributes to acute decompensated heart failure. Atibuclimab (IC14) is a monoclonal antibody blocking CD14, an inflammatory mediator associated with adverse cardiovascular outcomes. In this phase Ib, open-label, single-arm trial, adults hospitalized for acute decompensated heart failure with reduced ejection fraction and systemic inflammation received a single intravenous infusion of IC14. The primary endpoint was safety of IC14 treatment, whereas exploratory endpoints included CD14 receptor occupancy, C-reactive protein, B-type natriuretic peptide, and clinical outcomes. Atibuclimab was well tolerated, with no unexpected treatment-related serious adverse events. Treatment was associated with sustained CD14 receptor occupancy, reduction in systemic inflammation, lower natriuretic peptide levels, and improvement in left ventricular ejection fraction. These findings support the safety and biologic activity of CD14 blockade in acute decompensated heart failure and provide a rationale for progression to randomized phase II clinical trials.