Olamkicept up to 2400 mg safely tolerated in healthy men, showing dose-proportional exposure

Olamkicept is a first-in-class fully human fusion protein designed to selectively inhibit trans interleukin (IL)-6 signaling, a key pathway implicated in various inflammatory and autoimmune diseases. Current treatments for conditions like inflammatory bowel disease (IBD) often have limitations, driving the need for more targeted therapies. Previous Phase I trials established the safety of olamkicept at lower doses (up to 750 mg single, 600 mg multiple), with the 600 mg dose demonstrating clinical efficacy in IBD. This study aimed to extend the safety and pharmacokinetic profile to higher doses, exploring the potential for an expanded therapeutic window.

This Phase I, single-center, within-group randomized, double-blind, dose-extension trial investigated 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. Doses were administered as either SAD or MAD every 2 weeks over a 6-week period. The primary objective was to assess safety via treatment-emergent adverse events (TEAEs), vital signs, electrocardiogram, clinical chemistry, hematology, and hemostasis. Secondary outcomes included pharmacokinetics (PK) and immunogenicity. A total of 49 participants were randomized.

In the SAD part of the study, 4 treatment-emergent adverse events (TEAEs) and 1 adverse drug reaction were reported. The MAD part reported 16 TEAEs. Crucially, no treatment or dose-related trends were observed across any dose groups in any safety measure, indicating a favorable safety profile even at higher concentrations. Exposure to olamkicept increased in a dose-proportional manner across all tested doses, and there was no evidence of drug accumulation over the 6-week MAD period. This suggests predictable pharmacokinetics for olamkicept. However, an immunogenic response was noted: > New anti-olamkicept antibodies were identified in 4/18 participants (22.2%) across all dose levels in the MAD part, suggesting a subset of individuals may develop an immune response to the fusion protein.