First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis

• Published in: European journal of clinical pharmacology Vol. 72; no. 11; pp. 1303 - 1310
• Main Authors: Zhuang, Yanli, Calderon, Cesar, Marciniak, Stanley J, Bouman-Thio, Esther, Szapary, Philippe, Yang, Tong-Yuan, Schantz, Allen, Davis, Hugh M., Zhou, Honghui, Xu, Zhenhua
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2016; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - pharmacokinetics; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Clinical Trial; Dermatologic Agents - administration & dosage; Dermatologic Agents - adverse effects; Dermatologic Agents - blood; Dermatologic Agents - pharmacokinetics; Double-Blind Method; Female; Half-Life; Healthy Volunteers; Humans; Infusions, Intravenous; Injections, Subcutaneous; Interleukin-23 - antagonists & inhibitors; Interleukin-23 - immunology; Kinetics; Male; Middle Aged; Monoclonal antibodies; Pharmacology; Pharmacology/Toxicology; Psoriasis - blood; Psoriasis - drug therapy; Psoriasis - metabolism; Studies; Young Adult; Anti-interleukin-23; Monoclonal antibody; Safety; Pharmacokinetics; First-in-human; Guselkumab
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-016-2110-5

Purpose The purpose of this study is to evaluate the pharmacokinetics, immunogenicity, safety, and tolerability of guselkumab, a human monoclonal antibody with high affinity and specificity for binding to interleukin-23. Methods In this first-in-human, phase 1, randomized study, a single intravenous (IV; 0.03–10 mg/kg) or subcutaneous (SC; 10–300 mg) dose of guselkumab was administered to 47 healthy subjects, and a single SC dose (placebo, 10, 30, 100, 300 mg) was administered to 24 patients with moderate-to-severe psoriasis. Results Mean maximum observed serum concentration and area under the zero-to-infinity serum concentration-time curve of guselkumab increased in an approximately dose-proportional manner over the dose range of 0.03–10 mg/kg following a single IV administration or 10–300 mg following a single SC administration. Mean clearance and volume of distribution ranged from 3.62–6.03 mL/day/kg and 99.38–123.22 mL/kg, respectively. Mean half-life ranged from 12 to 19 days in healthy subjects and patients with psoriasis. Among guselkumab-treated subjects/patients, 1/30 (3.3 %) healthy subjects in the IV group, 0/6 healthy subjects in the SC group, and 1/20 (5.0 %) patients with psoriasis tested positive for antibodies to guselkumab. No clinically significant adverse events were identified in this study. Conclusion Guselkumab pharmacokinetic profiles were generally comparable between healthy subjects and patients with psoriasis. Guselkumab, administered as an IV infusion or SC injection, was well tolerated in healthy subjects and patients with psoriasis.