期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 94, 期 5, 页码 593-600出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/clpt.2013.150
关键词
-
资金
- European Union [261468]
- Opsona Therapeutics, Republic of Ireland
Upregulation of Toll-like receptor 2 (TLR2) plays a critical role in inflammation associated with ischemia/reperfusion-induced tissue damage. OPN-305 is the first humanized IgG4 monoclonal antibody against TLR2 in development and is intended for the prevention of reperfusion injury following renal transplantation and other indications. A phase I, single-center, prospective randomized, double-blind, placebo-controlled study was performed to evaluate single ascending doses of OPN-305 in 41 healthy male subjects (age range: 19-58 years) randomized to OPN-305 or placebo across six cohorts. OPN-305 was well tolerated across all doses, with no elevations in endogenous cytokines. A dose-proportional increase in maximum serum concentration (C-max) was observed, with area under the curve increasing in a greater-than- dose-proportional manner with increasing elimination half-life. OPN-305 produced full TLR2 receptor blockade on CD14(+) CD45(+) cells (monocytes), from 14 (0.5 mg/kg) to >90 (10 mg/kg) days, with a linear effect on the duration of inhibition of interleukin-6 release after TLR2 stimulation.
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