A multiple ascending dose, phase1b study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of lesigercept, a long-acting IgETrap-Fc fusion protein, in participants with atopy or allergic diseases

초록

Background: Lesigercept (also known as YH35324) has shown favorable safety, dose-proportional pharmacokinetics (PK), and sustained suppression of serum free immunoglobulin E (IgE) after single dosing in participants with atopy. We examined these outcomes following repeated dosing in participants with atopy or allergic diseases. Methods: In this phase 1b study, healthy adults who had atopy, with or without mild allergic diseases, and had serum total IgE level >= 30 IU/mL (Cohorts 1-4), and adults with moderate-to-severe atopic dermatitis (Cohort 5), were enrolled and randomized. Cohorts 1, 2, and 4 received lesigercept (0.75 mg/kg at 2-week intervals [Q2W], 3 mg/kg at 4-week intervals [Q4W], and 6 mg/kg at 8-week intervals [Q8W], respectively) or placebo (6:1). Cohort 3 received lesigercept (6 mg/kg Q4W), placebo, or omalizumab (300 mg Q4W) (6:1:6). Cohort 5 received lesigercept (6 mg/kg Q2W) or placebo (2,1). All cohorts were followed for 141 days. Results: Across Cohorts 1-4, participants received lesigercept (n = 25), omalizumab (n = 6), or placebo (n = 5); Cohort 5 received lesigercept (n = 6) or placebo (n = 3). Treatment-emergent adverse events (TEAEs) occurred in 15 participants in Cohorts 1-4 (lesigercept: 36.0%, omalizumab: 50.0%, placebo: 60.0%) and in 5 participants in Cohort 5 (lesigercept: 83.3%, placebo: 0%). No drug-related grade >= 3 or serious TEAEs, discontinuation, death, or anaphylaxis occurred. Lesigercept exposure (Cmax and AUClast) increased dose-dependently, and serum free IgE levels were suppressed in all lesigercept groups, with longer median durations below 25 ng/mL than placebo (10-29 versus 0 days). Conclusion: Lesigercept exhibited favorable safety, predictable PK, and durable serum free IgE suppression after repeated dosing, supporting further clinical development.

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