# Safety, tolerability, pharmacokinetics, and pharmacodynamics of KN060, a humanized anti-FXI/FXIa dual-domain antibody, following single ascending doses in healthy Chinese subjects

## TL;DR

KN060, a new antibody targeting blood clotting factors, was found safe and effective in healthy volunteers, showing potential for preventing thromboembolic diseases.

## Contribution

KN060 is a novel humanized dual-domain antibody targeting FXI/FXIa, evaluated for safety and pharmacokinetics in healthy Chinese subjects.

## Key findings

- KN060 was well tolerated with no significant adverse events.
- Pharmacokinetic data showed predictable drug levels and a positive correlation with clotting time prolongation.
- Immunogenicity analysis found no antidrug antibodies in subjects.

## Abstract

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.

This study aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous administration of KN060 in healthy Chinese subjects.

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.

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 Tmax 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.

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.

https://www.chictr.org.cn, identifier: ChiCTR2200056926; http://www.chinadrugtrials.org.cn, identifier: CTR20222339.

•KN060 is a new humanized dual-domain antibody developed to prevent blood clots by targeting factor (F)XI/FXIa.•This study tested a single intravenous dose of KN060 in healthy Chinese adults.•KN060 was safe, well tolerated, and showed predictable drug levels in the body.•KN060 prolonged blood clotting time, suggesting promise for preventing blood clots.

KN060 is a new humanized dual-domain antibody developed to prevent blood clots by targeting factor (F)XI/FXIa.

This study tested a single intravenous dose of KN060 in healthy Chinese adults.

KN060 was safe, well tolerated, and showed predictable drug levels in the body.

KN060 prolonged blood clotting time, suggesting promise for preventing blood clots.