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

作者：Na Li, Sepehr Shakib, Weilin Qian, Xiaoyan Yao, Puyuan Li, Tsz Keung Nip, Xiaoyan Bai, Kai Shen · 发表于：Clinical and Translational Science · 年份：2024 · DOI：10.1111/cts.13763 · 被引用次数：3 · 研究领域：Asthma and respiratory diseases、Urticaria and Related Conditions、Dermatology and Skin Diseases

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 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...