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Introduction <p>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.</p> Methods <p>This first-in-human, double-blind, phase&#xa0;1 trial of firsekibart included healthy Chinese participants (≥ 18 to ≤ 50&#xa0;years old) divided into five dose-escalated groups: 0.3, 1.0, 2.0, 4.0, and 6.0&#xa0;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.</p> Results <p>A total of 40 participants were enrolled in the study, receiving either firsekibart (<i>n</i> = 30) or placebo (<i>n</i> = 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 sampling timepoint increased proportionally with dose (0.3–6.0&#xa0;mg/kg). The area under the concentration–time curve from zero to infinity (AUC<sub>0–∞</sub>) showed a linear relationship with the dose of firsekibart. Overall, there were no treatment or dose-related trends observed in PD parameters, and no significant correlation was found between PK parameters and total serum IL-1β levels.</p> Conclusion <p>Firsekibart had an acceptable safety profile and was well tolerated in healthy Chinese participants across all investigated doses, supporting future investigation of firsekibart as a potential treatment option for inflammatory diseases.</p> Trial Registration <p>ClinicalTrials.gov NCT04337437 (retrospectively registered on April 7, 2020).</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月25日

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  • Hongzhong Liu,
  • Yuping Yuan,
  • Wei Tian,
  • Tianhong Luo,
  • Qian Xu,
  • Xiaoyan Zhu,
  • Rui Chen

摘要

Introduction

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.

Methods

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.

Results

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 sampling timepoint increased proportionally with dose (0.3–6.0 mg/kg). The area under the concentration–time curve from zero to infinity (AUC0–∞) showed a linear relationship with the dose of firsekibart. Overall, there were no treatment or dose-related trends observed in PD parameters, and no significant correlation was found between PK parameters and total serum IL-1β levels.

Conclusion

Firsekibart had an acceptable safety profile and was well tolerated in healthy Chinese participants across all investigated doses, supporting future investigation of firsekibart as a potential treatment option for inflammatory diseases.

Trial Registration

ClinicalTrials.gov NCT04337437 (retrospectively registered on April 7, 2020).