Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Olamkicept up to 2400 mg in Healthy Men: Phase I, Randomized, Placebo‐Controlled, and Double‐Blind Trial

Olamkicept is a first-in-class fully human fusion protein that selectively inhibits trans interleukin (IL)-6 signaling. Previous phase I clinical trials demonstrated that single doses up to 750 mg and multiple doses up to 600 mg were safe and well tolerated in healthy men and women. The clinical efficacy of the 600 mg dose has been demonstrated in inflammatory bowel disease. This phase I, single-center, within-group randomized, double-blind, dose-extension trial examined the safety, pharmacokinetics (PK), and immunogenicity of single (SAD) and multiple ascending doses (MAD) of olamkicept. Healthy men aged 18-45 years were randomized 3:1 in panels of eight individuals to receive either olamkicept (1200 mg, 1800 mg, or 2400 mg) or placebo as either SAD or MAD every 2 weeks over a 6-week period. The primary objective was to assess the safety of olamkicept based on treatment-emergent adverse events, vital signs, electrocardiogram, clinical chemistry, hematology, and hemostasis. Secondary outcomes included PK and immunogenicity. Forty-nine participants were randomized. Four treatment-emergent adverse events (TEAEs) and one adverse drug reaction were reported in the SAD, and 16 TEAEs were reported in the MAD part. No treatment or dose-related trends were observed across dose groups in any safety measure. Exposure increased in a dose-proportional manner and there was no evidence of accumulation. New anti-olamkicept antibodies were identified in 4/18 participants (22.2%) across all dose levels in the MAD part. SAD and MAD administration of up to 2400 mg olamkicept were well tolerated by healthy men and demonstrated dose-proportional increases in exposure.