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...

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Published in:Clinical pharmacology and therapeutics Vol. 94; no. 5; pp. 593 - 600
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 01.11.2013
Subjects:
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
Online Access:Get full text
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Summary: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
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ISSN:0009-9236
1532-6535
1532-6535
DOI:10.1038/clpt.2013.150