Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Analysis for Clazakizumab in Patients With End-Stage Kidney Disease Undergoing Dialysis.

ABSTRACT: The inflammatory cytokine interleukin-6 (IL-6) plays a significant role in the progression of cardiovascular disease (CVD). We evaluated the impact of clazakizumab, a monoclonal antibody targeting the IL-6 ligand, upon high-sensitivity C-reactive protein (hs-CRP) as part of the dose-finding phase 2b trial. In this randomized, double-blind trial, adults with cardiovascular disease and/or diabetes receiving maintenance dialysis and having hs-CRP ≥ 2 mg/L at baseline received clazakizumab (2.5 mg, 5 mg, or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. These data were used to develop a population pharmacokinetics (popPK) and a longitudinal PK-pharmacodynamic (PK-PD) model to characterize the relationship between clazakizumab and hs-CRP to support Phase 3 dose selection. A 2-

SUBMITTER: Muthukrishnan VY 

PROVIDER: S-EPMC12580930 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature