Pharmacokinetics, safety and preliminary efficacy of conbercept eye drops for corneal neovascularization: Results from phase I/IIa studies

AIMS: Vascular endothelial growth factor (VEGF) drives corneal neovascularization (CorNV), yet no anti-VEGF eye drops are clinically available. We report phase I/IIa trials of KH906, a novel topical anti-VEGF agent. METHODS: Trial 1 was a phase I, open-label, dose-escalation study in healthy adults receiving KH906 at 0.1, 0.5, or 1.0 mg/mL. Trial 2 was a phase I, multicentre, open-label, dose-escalation study in patients with CorNV at the same doses. Trial 3 was a phase IIa, randomized, double-masked, placebo-controlled study assigning patients 1:1:1 to 0.5 mg/mL KH906, 1.0 mg/mL KH906, or placebo. Primary endpoints were safety, tolerability and pharmacokinetics (Trials 1 and 2) and safety, tolerability and efficacy (Trial 3). RESULTS: From 10 December 2018 to 16 June 2021, 18 healthy participants and 39 patients with CorNV were enrolled. One treatment-related adverse event occurred: a mild corneal epithelial defect in the 1.0-mg/mL group in Trial 3. No serious or other drug-related adverse events were observed. In Trial 2, KH906 reduced the CorNV area and vessel length. In Trial 3, at Day 28, mean changes in CorNV area were -1.2 (0.8), -1.6 (1.1) and -0.7 (1.1), and mean changes in CorNV length were -8.0 (7.3), -6.6 (5.9) and -1.7 (7.9), in the 0.5-mg/mL KH906, 1.0-mg/mL KH906 and placebo groups, respectively. The 1.0-mg/mL dose produced greater reduction of the CorNV area than lower doses, indicating a dose-response effect. CONCLUSIONS: KH906 appears safe and well tolerated and demonstrates preliminary efficacy in reducing CorNV, with higher doses showing greater effect, supporting further clinical development.