Pharmacokinetics, Safety and Tolerability of Intravenous Lenzilumab, an Anti-GM-CSF Monoclonal Antibody Drug, in Healthy Korean Subjects.

Background: Lenzilumab is a recombinant monoclonal antibody neutralizing human granulocyte macrophage-colony stimulating factor. By modulating proinflammatory cytokine cascade, lenzilumab is expected to be effective in prevention and treatment of cytokine release syndrome. This study aimed to assess the safety, tolerability and pharmacokinetics (PKs) after a single intravenous (IV) administration of lenzilumab in healthy Korean subjects. Methods: A randomized, double-blind, placebo-controlled, single ascending dose study was conducted. The subjects received a single dose of 1, 3 or 10 mg/kg of lenzilumab or placebo via 1-hour IV infusion. Plasma samples for PK analysis were collected up to 69 days after the administration. PK parameters were estimated using noncompartmental analysis and dose-proportionality of lenzilumab was assessed. Adverse events and other safety variables were monitored throughout the whole study period. Results: Among the 20 subjects who completed the study, three received 1 mg/kg of lenzilumab, while six received 3 mg/kg and another six received 10 mg/kg. The remaining five subjects received the placebo. After 1-hour IV infusion, the maximum concentrations of lenzilumab were observed between 2.0 and 3.0 hours. The time-concentration profile of lenzilumab displayed biphasic decline and the terminal half-life ranged from 25.33 to 31.21 days. Lenzilumab exhibited a dose-proportional increase in its systemic exposure across 1 to 10 mg/kg. Nine cases of treatment-emergent adverse events occurred in six subjects receiving lenzilumab. All were mild and spontaneously recovered. Conclusion: The systemic exposure of lenzilumab was dose-proportional across 1 to 10 mg/kg in healthy Korean subjects. A single IV administration of lenzilumab was safe and well tolerated in the dose range between 1 and 10 mg/kg.