Safety and pharmacokinetics of a chimerized anti-lipoteichoic acid monoclonal antibody in healthy adults

Int Immunopharmacol. 2009 May;9(5):639-44. doi: 10.1016/j.intimp.2009.02.008. Epub 2009 Mar 5.

Abstract

A chimerized (murine/human) monoclonal antibody (pagibaximab) against lipoteichoic acid (LTA) and protective in animal models for coagulase-negative staphylococci (CONS) and Staphylococcus aureus bacteremia, was developed for prevention of staphylococcal infection in high-risk populations. This open label two-dose study of a single intravenous dose of 3 or 10 mg/kg of pagibaximab evaluated the safety/tolerability, pharmacokinetics, and opsonophagocytic activity of pagibaximab in healthy adults. Eight participants were enrolled (four in each dose group). No infusion, drug, or dose related adverse events occurred. Serum anti-LTA levels were dose-related; mean concentrations peaked at 87.75 and 259.24 microg/mL for 3 and 10 mg/kg groups, respectively. The half-life (beta) of pagibaximab was approximately 33 days. Opsonophagocytic activity of serum samples on a human clinical isolate of Staphylococcus epidermidis in a standard bacterial killing assay was dose-related, and peaked at a mean of 88.5 and 95.5% at 1:90 dilution for 3 and 10 mg/kg groups, respectively. Serum anti-LTA and opsonophagocytic activity levels exhibited statistically significant correlation. The results suggest that pagibaximab at 3 and 10 mg/kg administered as a single intravenous dose in healthy adults appears to: 1) provide preliminary safety and tolerability data, 2) produce dose-related serum anti-LTA and opsonophagocytic activity levels, 3) have a half-life similar to other immunoglobulin G1 antibodies, 4) exhibit statistically significant correlation between serum anti-LTA and opsonophagocytic activity levels. This study supports conducting safety and pharmacokinetic trials of pagibaximab in populations at high-risk of developing CONS infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Female
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Lipopolysaccharides / immunology*
  • Male
  • Mice
  • Middle Aged
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Neutrophils / microbiology
  • Neutrophils / pathology
  • Phagocytosis / drug effects
  • Phagocytosis / immunology
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / pharmacokinetics
  • Serum Bactericidal Test
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / therapy*
  • Staphylococcus aureus / immunology*
  • Staphylococcus epidermidis / immunology*
  • Teichoic Acids / immunology*

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Lipopolysaccharides
  • Recombinant Fusion Proteins
  • Teichoic Acids
  • pagibaximab
  • lipoteichoic acid