Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Firsekibart, an Anti-interleukin-1β Monoclonal Antibody, in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study

作者：Hongzhong Liu, Yuping Yuan, Wei Tian, Tian‐Hong Luo, Qian Xu, Xiaoyan Zhu, Rui Chen · 发表于：Advances in Therapy · 年份：2025 · DOI：10.1007/s12325-025-03279-4 · 被引用次数：6 · 研究领域：Inflammasome and immune disorders、Psoriasis: Treatment and Pathogenesis、Rheumatoid Arthritis Research and Therapies

The pro-inflammatory cytokine interleukin-1β (IL-1β) is an important therapeutic target for treating autoinflammatory diseases. Firsekibart is a high affinity, fully human monoclonal antibody targeting IL-1β, which selectively binds to and neutralizes IL-1β. Here, we investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of firsekibart administered as a single-dose, subcutaneous injection in healthy Chinese participants. This first-in-human, double-blind, phase 1 trial of firsekibart included healthy Chinese participants (≥ 18 to ≤ 50 years old) divided into five dose-escalated groups: 0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg. In each group, participants were randomized in a 3:1 ratio to receive firsekibart or placebo. The primary endpoint was the safety and tolerability, primarily assessed by monitoring adverse events (AEs). Secondary endpoints included the evaluation of immunogenicity, PK, and PD. A total of 40 participants were enrolled in the study, receiving either firsekibart ( n = 30) or placebo ( n = 10); all participants completed the study. Treatment-emergent AEs (TEAEs) occurred in 86.7% of participants receiving firsekibart and 90.0% receiving placebo. There were no reports of grade ≥ 3 TEAEs, serious AEs, or TEAEs leading to study withdrawal or death. The incidence of TEAEs in the firsekibart group was not dose dependent. No PK/PD changes or safety events related to immunogenicity were observed. Serum concentration of firsekibart at each...