Safety, tolerability, and pharmacokinetics of HL-300, a novel topical Pan-JAK inhibitor, in healthy Chinese adults: a first-in-human, randomized, double-blind, placebo-controlled phase I trial

INTRODUCTION: HL-300 is a novel topical pan-JAK inhibitor ointment targeting JAK1, JAK2, JAK3, and TYK2, developed for inflammatory skin diseases like atopic dermatitis. This first-in-human (FIH) study evaluated the safety, tolerability, and pharmacokinetic (PK) profiles of single and multiple topical doses of HL-300 in healthy Chinese adults. METHODS: We conducted a single-center, randomized, double-blind, placebo-controlled phase I trial. Thirty-six subjects received HL-300 (0.25%, 0.5%, 1.0%) or placebo across single-dose (6.25-50 mg) and multiple-dose (50 mg BID for 7 days) groups. Plasma concentrations were analyzed for PK parameters. Safety assessments included adverse events (AEs), laboratory tests, vital signs, ECGs, and skin reactions. RESULTS: accumulation ratios were 40.93 and 18.9, respectively. Most TEAEs were grade 1, with no serious AEs observed. CONCLUSION: HL-300 was generally safe and well tolerated after single and multiple topical administrations in healthy Chinese adults, with no serious adverse events or clear dose-related safety risks observed. PK results showed slow percutaneous absorption, low systemic exposure after single dosing, and attainment of steady state with some accumulation after multiple dosing, while the overall safety profile remained acceptable. These findings support further phase II clinical development of HL-300 and provide a basis for dose optimization and efficacy evaluation in patients with AD and other inflammatory skin diseases.