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April 22, 2026Diabetes Obesity and Metabolism0 citations

A Phase 1, Randomised, Double‐Blind, Placebo‐Controlled Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of KN069 (a Dual GLP ‐ 1R Agonist and GIPR Antagonist) in Male Adults With Overweight or Obesity

JXJinlian XieCentral South University JHJie HuangCentral South University QWQian WuCentral South University

Key Points

This study aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KN069 in men with overweight or obesity.
Randomised, double-blind, placebo-controlled trial design
Single ascending dose (SAD) and multiple ascending dose (MAD) phases were conducted
Safety assessed through adverse events and pharmacokinetics analyzed using ELISA.
KN069 was well tolerated with mild gastrointestinal adverse events, showing no severe complications.
Dose-proportional pharmacokinetics were observed, with a long total half-life of 899.74–1099.01 hours.
Significant weight reductions were noted in the SAD and MAD groups, with metabolic improvements in glucose and insulin levels.

Abstract

ABSTRACT Aims This first‐in‐human Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of KN069, a novel dual Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA)/Glucose‐dependent insulinotropic polypeptide receptor (GIPR) antagonist in Chinese men with overweight/obesity. Materials and Methods This randomised, double‐blind trial included a single ascending dose (SAD; 12–120 mg, N = 36, 3:1 active‐to‐placebo) and a multiple ascending dose (MAD; N = 12, dose escalation 15–60 mg) phase. Safety was assessed via adverse events (AEs) and compliance. PK was analysed using a sandwich enzyme‐linked immunosorbent assay (ELISA) for Intact and Total KN069. PD included measurements of body weight, waist circumference, body mass index (BMI) and metabolic parameters. Immunogenicity was assessed by detecting anti‐drug antibodies (ADA). Results KN069 was well tolerated, with predominantly mild‐to‐moderate gastrointestinal adverse events. PK showed dose‐proportional exposure (12–90 mg) with a long half‐life for Total KN069 (899.74–1099.01 h). In the SAD part, preliminary dose‐dependent weight reductions were observed, with maximum early changes at Day 7 (90 mg: −4.71% vs. placebo: −0.41%) and sustained for up to 133 days. In the MAD part, Group B (60 mg) achieved a −2.57% mean weight reduction from baseline at Day 25, alongside a significant decrease in waist circumference ( p = 0.0446). Metabolic improvements included lower fasting glucose, triglycerides, uric acid and elevated insulin/C‐peptide. Conclusions KN069 exhibits favourable safety, long‐acting PK and preliminary dose‐dependent weight reduction alongside expected pharmacologic metabolic effects, supporting further clinical development. ClinicalTrials.gov Identifier: NCT06547775.

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