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 ...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 2.0µg/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 45µg/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 45µg/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 206h 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 45μg/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.展开更多
文摘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 2.0µg/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 45µg/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 45µg/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 206h 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 45μg/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.
