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

The first-in-class, fully human fusion protein, olamkicept, selectively inhibits trans interleukin-6 signaling. Previously, the safety, tolerability, pharmacokinetics (PK), and immunogenicity of olamkicept following single ascending doses (SAD) up to 750 mg and multiple ascending doses (MAD) up to 600 mg daily were assessed. To assess higher doses, parallel trials of olamkicept up to 2400 mg daily were separately performed in healthy European and Japanese adult men. In this phase I, single-center, within-group randomized, double-blind trial, Japanese participants were randomized to SAD olamkicept infusions (1200, 1800, and 2400 mg) or placebo. The primary objective was to assess the safety of higher doses of olamkicept based on treatment-emergent adverse events (TEAEs), vital signs, electrocardiograms (ECG), and clinical chemistry. PK parameters were included as secondary outcomes. Immunogenicity was not assessed in the present Japanese cohort. Twenty-four participants were randomized. Four TEAEs and no adverse drug reactions were reported. All TEAEs were mild and resolved without intervention. There were no treatment or dose related trends in TEAEs, vital signs, ECG, clinical chemistry, hematology, hemostasis, or urinalysis. A single infusion of olamkicept achieved measurable serum concentrations for up to 28 days after treatment and exposure was dose proportional. In conclusion, single doses of olamkicept up to 2400 mg have a favorable safety profile and dose proportional PK in healthy Japanese men. Trial Registration: ClinicalTrials.gov identifier: NCT06515834.