Randomized, Double-Blind, Placebo-Controlled, Phase I Study Of The Safety And Pharmacokinetics Of Namilumab In Healthy Japanese And Caucasian Men

Objective: Namilumab is an investigational human monoclonal antibody to human granulocyte-macrophage colony-stimulating factor (GM-CSF). A phase I study of repeated namilumab dosing (150 or 300 mg subcutaneously) in non-Japanese patients with rheumatoid arthritis reported no safety concerns. The objective of this study was to report the safety (primary endpoint) and pharmacokinetic/pharmacodynamic effects of namilumab in healthy Japanese and Caucasian men aged 20 - 45 years (NCT02354599). Materials and methods: 24 Japanese subjects were randomized to a single dose of namilumab (80, 150, or 300 mg; n = 6/group) or placebo (n = 6; 2 subjects randomized/ matched dose); 8 Caucasian subjects received namilumab 150 mg (n = 6) or placebo (n = 2). Results: Overall, 29 subjects completed the study (2 withdrew voluntarily; 1 due to a serious adverse event (AE) unrelated to treatment). Baseline demographics were similar across treatment groups; mean age and weight were higher in Caucasians. Namilumab was well tolerated, with no notable safety concerns or pharmacokinetic/pharmacodynamic differences between Japanese and Caucasian subjects. AEs were mild to moderate, with no dose-proportional increase in Japanese subjects. Area under the serum concentration-time curve from zero to infinity (AUC(0-infinity)) and maximum serum concentration (C-max) increased in a dose-proportional manner in Japanese subjects. AUC(0-infinity), was similar in Japanese (575.2 mu gxday/mL) and Caucasian (559.7 mu gxday/mL) 150-mg groups. C-max was similar to 40% higher in Japanese subjects. Mean plasma total GM-CSF concentration-time profiles were similar in the Japanese and Caucasian 150-mg groups. Namilumab induced no clinically-relevant antibody response. Conclusion: Namilumab was well tolerated in Japanese and Caucasian subjects; namilumab 150 mg had similar pharmacokinetics in both populations, supporting further clinical development of this dose.