Randomized, Double‐Blind, Placebo‐Controlled, Dose‐Escalating Phase I, Healthy Subjects Study of Intravenous OPN‐305, a Humanized Anti‐TLR2 Antibody

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 t...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Clinical pharmacology and therapeutics Ročník 94; číslo 5; s. 593 - 600
Hlavní autoři:	Reilly, M, Miller, R M, Thomson, M H, Patris, V, Ryle, P, McLoughlin, L, Mutch, P, Gilboy, P, Miller, C, Broekema, M, Keogh, B, McCormack, W, Wetering de Rooij, J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.11.2013
Témata:	Adolescent Adult Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacokinetics Antibodies, Monoclonal - pharmacology Dose-Response Relationship, Immunologic Double-Blind Method Humans Infusions, Intravenous Interleukin-6 - antagonists & inhibitors Interleukin-6 - blood Leukocyte Count Male Middle Aged Toll-Like Receptor 2 - immunology Young Adult
ISSN:	0009-9236, 1532-6535, 1532-6535
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	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 (Cmax) 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. Clinical Pharmacology & Therapeutics (2013); 94 5, 593–600. doi:10.1038/clpt.2013.150
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0009-9236 1532-6535 1532-6535
DOI:	10.1038/clpt.2013.150