Safety, pharmacokinetics, and pharmacodynamics of anti-IL-4Rα antibody SHR-1819 in healthy subjects: A randomized, controlled phase I study.

SHR-1819 is a novel anti-IL-4Rα monoclonal antibody currently under clinical development for use in patients with type 2 inflammatory diseases. In this randomized, double-blind, placebo-controlled, single-dose escalation phase I trial, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-1819 in healthy subjects. Subjects received a single subcutaneous injection of SHR-1819 or placebo, with dose escalation starting at 60 mg and subsequently increasing to 120, 240, 360, and 720 mg. A total of 42 eligible subjects were randomized, and 33 received SHR-1819 (1 subject in the 60 mg cohort and 8 subjects each in the 120, 240, 360 , and 720 mg cohorts) and 9 received placebo. SHR-1819 was well-tolerated, with the majority of adverse events being mild in severity. The exposure of SHR-1819 increased in a manner greater than proportionally with a dose range of 120 to 720 mg. The median T max was within 4-7 days (60-720 mg), and the mean half-life ranged from 2.88 to 5.97 days (120-720 mg). The clearance rate of SHR-1819 exhibited a decrease with increasing dose level. Administration of SHR-1819 resulted in a certain degree of reduction in the percentage change from baseline in concentrations of inflammatory biomarkers TARC/CCL17 and IgE, while the reduction of TARC/CCL17 concentrations showed a dose-dependent trend. More than half of the total subjects treated with SHR-1819 were reported antidrug antibody-negative. The preliminary data from this phase I study support further development of SHR-1819 for the treatment of type 2 inflammatory diseases.