Safety, pharmacokinetics and population pharmacokinetic model of TQH2722, a novel IL-4Rα monoclonal antibody in healthy subjects: a phase I, first-in-human, single-dose and multiple-dose escalation study

Abstract

The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics (PK) of TQH2722, an Interleukin-4 receptor alpha (IL-4Rα) monoclonal antibody, in healthy subjects. In this randomized, double-blind and placebo-controlled trial, TQH2722 was subcutaneously injected as single-ascending dose (n = 46; 50, 150, 300, 600 and 1200 mg) or multiple-ascending dose (n = 20; 150 and 600 mg; four doses every 2 weeks). Subjects were monitored for adverse events and blood samples were collected for pharmacokinetics. A population pharmacokinetic model was developed and validated. TQH2722 was well tolerated with no serious or severe adverse events observed. After a single dose, the maximum concentration occurred at 3-7 days, with t_1/2 ranged from 2.65 to 17.43 days. Four repeated dosing caused about 3-fold degree of accumulation for C_max and AUC. Regardless of single or multiple doses, the exposure showed a nonlinear and greater than dose proportional increase. A two-compartment model taking into account the mechanistic target-mediated drug disposition process with parallel linear and nonlinear Michaelis-Menten (MM) elimination and first-order absorption well described the pharmacokinetics of TQH2722. In conclusion, TQH2722 was safe and well tolerated, and its PK profiles were well characterized, supporting its further clinical development in patients.