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

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.

IL-4Rα monoclonal antibody; Pharmacokinetics; Phase I; Population pharmacokinetic model; Safety; TQH2722.