Abstract
BACKGROUND: KN060 is a humanized dual-domain antibody targeting coagulation factor XI (FXI) and factor XIa (FXIa) and is currently being developed for the prevention of thromboembolic diseases. OBJECTIVES: This study aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous administration of KN060 in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled clinical study was conducted in 38 healthy Chinese subjects. The study included 6 dose groups (0.1, 0.3, 1.0, 2.5, 5.0, and 10.0 mg/kg), with KN060 administered via a single ascending-dose regimen. RESULTS: KN060 demonstrates good tolerability and safety, with no significant treatment-emergent adverse events. A single intravenous infusion of KN060, ranging from 0.1 to 10.0 mg/kg, resulted in an average T (max) ranging from 1.02 to 3.34 hours. For a dose range of 0.3 to 10.0 mg/kg, the average half-life ranged from 122.96 to 146.47 hours. Pharmacokinetic and pharmacodynamic analyses revealed that within the dose range of 0.1 to 10.0 mg/kg, drug concentration was positively correlated with activated partial thromboplastin time and negatively correlated with factor (F)XI activity and free FXI content. Immunogenicity analysis showed that all subjects were negative for antidrug antibodies. CONCLUSION: The study results demonstrated that KN060 was well tolerated and safe. Based on pharmacokinetic and pharmacodynamic data, KN060 is a promising humanized dual-domain antibody simultaneously targeting FXI/FXIa for the prevention of thromboembolic diseases. TRIAL REGISTRATION: https://www.chictr.org.cn, identifier: ChiCTR2200056926; http://www.chinadrugtrials.org.cn, identifier: CTR20222339.