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.
Abstract
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.