A Randomized, Double‐Blind, Placebo‐Controlled, Multiple Ascending Dose Phase 1 Study of Firsekibart in Chinese Healthy Participants

Abstract Firsekibart is an anti‐IL‐1β monoclonal antibody for treating acute gout flares in adults. This randomized, double‐blind, placebo‐controlled study assessed the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple ascending doses of firsekibart in healthy Chinese adults. Participants were assigned to one of the two firsekibart cohorts (120 or 200 mg) every 4 weeks for three doses and randomized in a 5:1 ratio to receive firsekibart or placebo. Twenty‐four participants completed the study. After a single dose, the median T max was 7.0 days for both firsekibart groups. Mean C max was 16.0 and 29.2 µg/mL; AUC 0–t was 350.6 and 600.0 d·µg/mL for the 120 and 200 mg groups. Following multiple doses, the median T max,ss was 4.0 days and 5.5 days, C max,ss was 31.5 and 54.1 µg/mL, AUC 0–t,ss was 1213.3 and 1975.8 d·µg/mL, and AUC 0–∞,ss was 1445.3 and 2355.4 d·µg/mL. Accumulation ratios for C max and AUC were <2 in both groups. Serum total IL‐1β levels showed no dose‐related trends and immunogenicity was low. Treatment‐emergent adverse events (TEAEs) occurred in 65.0% of firsekibart‐treated participants and 75.0% of placebo‐treated participants. TEAEs were mostly grade 1 or 2. Firsekibart was safe, well tolerated after multiple administrations in healthy participants, with dose‐proportional exposure and modest accumulation.