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

Abstract

Abstract 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 Tmax 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.