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

Authors :
Leonard E. Weisman
William Kramer
James J. Mond
George T. Mandy
Karen Adams
Gerald W. Fischer
Helen M. Thackray
Karen E. Johnson
Beth E. Stratton
Richard F. Schuman
Source :
International Immunopharmacology. 9:639-644
Publication Year :
2009
Publisher :
Elsevier BV, 2009.

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.

Details

ISSN :
15675769
Volume :
9
Database :
OpenAIRE
Journal :
International Immunopharmacology
Accession number :
edsair.doi.dedup.....8fb28876affa6a6c5f4151ed20d11f71
Full Text :
https://doi.org/10.1016/j.intimp.2009.02.008