A phase 1, randomized, double-blind, placebo-controlled trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of KN056 (a recombinant human GLP-1 variant Fc fusion protein) in healthy Chinese participants.

Abstract

Background: This randomized clinical pharmacology trial investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of KN056 following single-dose subcutaneous administration in healthy Chinese participants.

Methods: Thirty healthy male subjects were randomized to receive a single dose of KN056 (0.5, 1.0, 3.0, 6.0, or 12.0 mg) or placebo. PK and PD parameters, as well as safety and tolerability, were assessed.

Results: KN056 exposure increased proportionally with dose, with a half-life ranging from 141 to 188 hours. KN056 was well-tolerated, with gastrointestinal adverse events being the most common, particularly at the highest dose (12.0 mg). In the oral glucose tolerance test, KN056 dose-dependently decreased the AUC on the glucose versus time (gAUC) from baseline within 144 hours post-dosing. Specifically, the maximum reduction was 29.9% (occurring at the 72-hour mark). Body weight decreased within seven days of administration, correlating with dose levels, with a mean reduction of -1.68 kg in the 12.0 mg group; however, no significant change in body weight was observed by the end of the study.

Conclusions: KN056 demonstrated favorable PK, PD, and safety profiles in healthy Chinese participants, supporting its potential for once-weekly dosing.