A phase I, randomized, dose-escalation clinical trial of the anti-IgE humanized monoclonal antibody LP-003 in healthy subjects.

Abstract

Introduction: Immunoglobulin (Ig) E is crucial in driving inflammatory responses that lead to clinical symptoms of atopy. LP-003, a humanized Ig G1 kappa monoclonal antibody, blocks the binding of human IgE to the FcεRI receptor and was developed for the treatment of uncontrolled atopy. In this phase I trial, a randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study was performed, and the safety, tolerability, pharmacokinetics (PK), and immunogenicity of LP-003 were assessed in healthy subjects.

Methods: The study consisted of two parts: the SAD component and the MAD component. In the SAD study, five dose cohorts were planned (0.3/1.0/3.0/6.0/10.0 mg/kg). In the MAD study, two dose cohorts (2.0/4.0 mg/kg) were planned.

Results: Most treatment-emergent adverse events (TEAEs) were mild or moderate, and their incidence was comparable between the LP-003 and placebo groups. The serum LP-003 concentration and PK exposures proportionally increased with dose level ranging from 0.3-10.0 mg/kg in SAD study and 2.0-4.0 mg/kg in MAD study, resulting in a prolonged serum half-life of ~70 days. The incidence of anti-drug antibodies (ADAs) was 12.5% in both SAD and MAD studies, showing no clear correlation with the dose or impact on safety.

Conclusion: LP-003 demonstrated a favorable safety profile and a superior PK advantage characterized by an extended half-life, supporting its development as a long-acting therapeutic option for allergic conditions.