A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis

Leonard E. Weisman, Helen M. Thackray, Robin H Steinhorn, William F. Walsh, Herbert A. Lassiter, Ramasubbareddy Dhanireddy, Beverly S. Brozanski, Kristine G H Palmer, Michael S. Trautman, Marilyn Escobedo, H. Cody Meissner, Pontthenkandath Sasidharan, Jennifer Fretz, John F. Kokai-Kun, William G. Kramer, Gerald W. Fischer, James J. Mond

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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. PATIENTS AND 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.

Original languageEnglish (US)
Pages (from-to)271-279
Number of pages9
JournalPediatrics
Volume128
Issue number2
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • Chimeric
  • Immunogenic
  • Immunoglobulin
  • Monoclonal antibody
  • Newborn
  • Nosocomial infection
  • Pharmacokinetics
  • Safety
  • Sepsis
  • Staphylococcus
  • Very low birth weight

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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