title: A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis.
abstract: BACKGROUND
  Pagibaximab, a human chimeric monoclonal antibody developed against lipoteichoic acid, was effective against staphylococci preclinically and seemed safe and well tolerated in phase 1 studies.
  
  
  OBJECTIVE
  To evaluate the clinical activity, pharmacokinetics, safety, and tolerability of weekly pagibaximab versus placebo infusions in very low birth weight neonates.
  
  
  METHODS
  A phase 2, randomized, double-blind, placebo-controlled study was conducted at 10 NICUs. Patients with a birth weight of 700 to 1300 g and 2 to 5 days old were randomly assigned to receive 3 once-a-week pagibaximab (90 or 60 mg/kg) or placebo infusions. Blood was collected for pharmacokinetics, bacterial killing, and safety analyses. Adverse event and clinical outcome data were collected.
  
  
  RESULTS
  Eighty-eight patients received pagibaximab at 90 (n = 22) or 60 (n = 20) mg/kg or placebo (n = 46). Groups were not different in demography, mortality, or morbidity. Pagibaximab demonstrated linear pharmacokinetics, a 14.5-day half-life, and nonimmunogenicity. Definite staphylococcal sepsis occurred in 0%, 20%, and 13% (P < .11) and nonstaphylococcal sepsis occurred in 0%, 10%, and 15% (P < .15) of patients in the 90 mg/kg, 60 mg/kg, and placebo groups, respectively. In all patients with staphylococcal sepsis, estimated or observed pagibaximab levels were <500 μg/mL (target level) at infection.
  
  
  CONCLUSIONS
  Three once-a-week 90 or 60 mg/kg pagibaximab infusions, in high-risk neonates, seemed safe and well tolerated. No staphylococcal sepsis occurred in infants who received 90 mg/kg. Target levels were only consistently achieved after 2 to 3 doses. Dose optimization should enhance protection.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2303, USA. lweisman@bcm.edu
authors.forename: Leonard E
authors.initials: LE
authors.lastname: Weisman
authors.forename: Helen M
authors.initials: HM
authors.lastname: Thackray
authors.forename: Robin H
authors.initials: RH
authors.lastname: Steinhorn
authors.forename: William F
authors.initials: WF
authors.lastname: Walsh
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Lassiter
authors.forename: Ramasubbareddy
authors.initials: R
authors.lastname: Dhanireddy
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Brozanski
authors.forename: Kristine G H
authors.initials: KG
authors.lastname: Palmer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Trautman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Escobedo
authors.forename: H Cody
authors.initials: HC
authors.lastname: Meissner
authors.forename: Pontthenkandath
authors.initials: P
authors.lastname: Sasidharan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fretz
authors.forename: John F
authors.initials: JF
authors.lastname: Kokai-Kun
authors.forename: William G
authors.initials: WG
authors.lastname: Kramer
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Fischer
authors.forename: James J
authors.initials: JJ
authors.lastname: Mond
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D012307:Risk Factors; D018805:Sepsis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; C524976:pagibaximab