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

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88 Scopus citations


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
Pages (from-to)271-279
Number of pages9
Issue number2
StatePublished - Aug 1 2011


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


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