药代动力学
耐受性
医学
药效学
药理学
安慰剂
免疫原性
内科学
不利影响
加药
免疫学
抗体
病理
替代医学
作者
Prafull Mistry,Juliet Reid,Isabelle Pouliquen,Simon McHugh,Lee Abberley,Stephen DeWall,Adam Taylor,Xin Tong,Marian Rocha del Cura,Elizabeth McKie
摘要
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK1070806, a novel IgG1 mAb that neutralizes human interleukin (IL)-18.In this first-timein-human (FTIH) study, cohorts of healthy and obese subjects were randomly allocated to receive single doses of GSK1070806 (0.008 - 10 mg/kg) or placebo. Blood was sampled ≤ 274 days post-dosing, and safety monitored.GSK1070806 was generally well tolerated. The most common AEs were nasopharyngitis and headache, arising as frequently in the placebo as in the active drug groups; most AEs were mild to moderate and unrelated to dose level. There were no allergic, delayed-type hypersensitivity, or infusion-related reactions and the incidence of immunogenicity was low. GSK1070806 plasma pharmacokinetic profiles were comparable in healthy and obese subjects; there was no major deviation from dose proportionality for AUC(∞) and C(max) although a trend for dose-dependent increase in t(1/2) was observed. Serum drug-bound IL-18 levels increased post-dosing and were sustained for a long time-period following GSK1070806 administration. Ex-vivo whole blood assay demonstrated prolonged pharmacological activity of GSK1070806 as determined by its primary immunological mechanism of action, inhibition of IL-18-induced IFN-γ production.GSK1070806 warrants clinical investigation in patients.
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