title: Phase II, randomized, double-blind, multicenter study comparing the safety and pharmacokinetics of tefibazumab to placebo for treatment of Staphylococcus aureus bacteremia.
abstract: Tefibazumab (Aurexis), a humanized monoclonal antibody that binds to the surface-expressed adhesion protein clumping factor A, is under development as adjunctive therapy for serious Staphylococcus aureus infections. Sixty patients with documented S. aureus bacteremia (SAB) were randomized and received either tefibazumab at 20 mg/kg of body weight as a single infusion or a placebo in addition to an antibiotic(s). The primary objective of the study was determining safety and pharmacokinetics. An additional objective was to assess activity by a composite clinical end point (CCE). Baseline characteristics were evenly matched between groups. Seventy percent of infections were healthcare associated, and 57% had an SAB-related complication at baseline. There were no differences between the treatment groups in overall adverse clinical events or alterations in laboratory values. Two patients developed serious adverse events that were at least possibly related to tefibazumab; one hypersensitivity reaction was considered definitely related. The tefibazumab plasma half-life was 18 days. Mean plasma levels were <100 microg/ml by day 14. A CCE occurred in six patients (four placebo and two tefibazumab patients) and included five deaths (four placebo and one tefibazumab patient). Progression in the severity of sepsis occurred in four placebo and no tefibazumab patients. Tefibazumab was well tolerated, with a safety profile similar to those of other monoclonal antibodies. Additional trials are warranted to address the dosing range and efficacy of tefibazumab.
authors.affiliation: Greenville Hospital Sytem University Medical Center, South Carolina, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Weems
authors.forename: James P
authors.initials: JP
authors.lastname: Steinberg
authors.forename: Scott
authors.initials: S
authors.lastname: Filler
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
authors.forename: G Ralph
authors.initials: GR
authors.lastname: Corey
authors.forename: Priya
authors.initials: P
authors.lastname: Sampathkumar
authors.forename: Lisa
authors.initials: L
authors.lastname: Winston
authors.forename: Joseph F
authors.initials: JF
authors.lastname: John
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Kubin
authors.forename: Rohit
authors.initials: R
authors.lastname: Talwani
authors.forename: Thomas
authors.initials: T
authors.lastname: Moore
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Patti
authors.forename: Seth
authors.initials: S
authors.lastname: Hetherington
authors.forename: Michele
authors.initials: M
authors.lastname: Texter
authors.forename: Eric
authors.initials: E
authors.lastname: Wenzel
authors.forename: Violet A
authors.initials: VA
authors.lastname: Kelley
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000628:therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal