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.
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引用次数: 0
Abstract
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).
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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