A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in patients with rheumatoid arthritis

Clenoliximab (IDEC-151) is a macaque-human chimeric monoclonal antibody (im munoglobulin G4) specific for the CD4 molecule on the surface of T lymphocy tes. It is being studied in patients with rheumatoid arthritis in which T c ell activation orchestrates inflammation and tissue damage. In this initial study in humans, the pharmacokinetics and pharmacodynamics of clenoliximab were investigated after single intravenous infusion. Blood was collected u p to 12 weeks after dose administration to measure clenoliximab concentrati on, CD4(+) T-cell count, CD4 antigen coating, and CD4 cell surface density. Clenoliximab displayed nonlinear pharmacokinetic behavior and caused an 80 reduction in CD4 density for up to 3 weeks, without depleting T cells. A p harmacokinetic-pharmacodynamic model Nas developed that described the relat ionship between antibody concentration, antigen coating, and the observed d ecreases in CD4 cell surface density. This was used to anticipate the effec ts of clenoliximab in untested regimens and optimize the design of future c linical trials.