title: Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody.
abstract: 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.
authors.affiliation: Opsona Therapeutics, Dublin, Republic of Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Reilly
authors.forename: R M
authors.initials: RM
authors.lastname: Miller
authors.forename: M H
authors.initials: MH
authors.lastname: Thomson
authors.forename: V
authors.initials: V
authors.lastname: Patris
authors.forename: P
authors.initials: P
authors.lastname: Ryle
authors.forename: L
authors.initials: L
authors.lastname: McLoughlin
authors.forename: P
authors.initials: P
authors.lastname: Mutch
authors.forename: P
authors.initials: P
authors.lastname: Gilboy
authors.forename: C
authors.initials: C
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Broekema
authors.forename: B
authors.initials: B
authors.lastname: Keogh
authors.forename: W
authors.initials: W
authors.lastname: McCormack
authors.forename: J
authors.initials: J
authors.lastname: van de Wetering de Rooij
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D000093242:Interleukin-6 Inhibitors; C495342:TLR2 protein, human; C585159:tomaralimab