Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects

• Published in: Cellular & molecular immunology Vol. 16; no. 5; pp. 473 - 482
• Main Authors: Tang, Kai-Yang, Lickliter, Jason, Huang, Zhi-Hua, Xian, Zong-Shu, Chen, Han-Yang, Huang, Cheng, Xiao, Chong, Wang, Yu-Peng, Tan, Ying, Xu, Lin-Feng, Huang, Yu-Liang, Yan, Xiao-Qiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2019; Nature Publishing Group
• Subjects: Adult; Amyloid; Antibodies; Bacterial Infections - drug therapy; Biomarkers; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; C-reactive protein; Chemokines; Clinical trials; Constant region; Cytokines; Cytokines - blood; Dimerization; Dosage; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Fusion protein; Healthy Volunteers; Humans; Immunoglobulin Constant Regions - genetics; Immunoglobulin G; Immunology; Inflammation Mediators - blood; Inflammatory diseases; Infusions, Intravenous; Injection; Injection Site Reaction - etiology; Interleukin 22; Interleukins - genetics; Intravenous administration; Male; Medical Microbiology; Microbiology; Pharmacodynamics; Pharmacokinetics; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - therapeutic use; Serum Amyloid A Protein - metabolism; Serum levels; Skin; Triglycerides; Vaccine; Wound Healing - drug effects; Young Adult; Pharmacodynamics; F-652; Safety; Pharmacokinetics; Interleukin-22
• ISSN: 1672-7681; 2042-0226; 2042-0226
• DOI: 10.1038/s41423-018-0029-8

F-652 is a recombinant fusion protein consisting of two human interleukin-22 (IL-22) molecules linked to an immunoglobulin constant region (IgG 2 -Fc). IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection. The safety, pharmacokinetics (PK), tolerability, and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized, double-blind, placebo-controlled study. Following single-dose subcutaneous (SC) injection of F-652 at 2.0 µg/kg into healthy subjects, six out of six subjects experienced delayed injection site reactions, which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing. F-652 was then administered to the healthy subjects via an intravenous (IV) infusion at 2.0, 10, 30, and 45 µg/kg. No severe adverse event (SAE) was observed during the study. Among the IV-dosed cohorts, eye and skin treatment emergent adverse events (TEAEs) were observed in the 30 and 45 µg/kg cohorts. F-652 IV dosing resulted in linear increases in C max and AUC (0– t ) , and the T 1/2 ranged from 39.4 to 206 h in the cohorts. An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A, C-reactive protein, and FIB, and decreased serum triglycerides. The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45 μg/kg. In conclusion, IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties. These results warrant further clinical development of F-652 to treat inflammatory diseases.