First-in-Man Study With Inclacumab, a Human Monoclonal Antibody Against P-selectin

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Immunology

Background:

• Atherosclerotic cardiovascular diseases (ASCVD) represent a significant global health burden.
• P-selectin plays a crucial role in the inflammatory processes underlying ASCVD.
• Inclacumab is a novel monoclonal antibody targeting P-selectin for potential ASCVD treatment.

Purpose of the Study:

• To evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of inclacumab.
• To assess the dose-dependent effects of inclacumab on P-selectin mediated pathways.
• To establish the tolerability and PK/PD relationship of inclacumab in healthy subjects.

Main Methods:

• A randomized, double-blind, placebo-controlled, single ascending dose study.
• Fifty-six healthy subjects received intravenous inclacumab (0.03-20 mg/kg) or placebo.
• Measurements included platelet-leukocyte aggregates, soluble P-selectin, drug concentrations, bleeding time, and platelet aggregation.

Main Results:

• Inclacumab exhibited dose-dependent inhibition of platelet-leukocyte aggregates and soluble P-selectin occupancy.
• Pharmacokinetic profiles suggested target-mediated drug disposition.
• Inclacumab was well tolerated, with no significant impact on bleeding time or platelet aggregation.

Conclusions:

• Inclacumab demonstrated a favorable safety profile and predictable PK/PD relationship in healthy subjects.
• The observed dose-dependent inhibition of P-selectin pathways supports its potential therapeutic utility in ASCVD.
• These findings provide a basis for further clinical development in patient populations.