†Carlos Milla, MD, Center for Excellence in Pulmonary Biology, Stanford University, Palo Alto, CA; James F. Chmiel, MD, Rainbow Babies and Children's Hospital, Cleveland, OH; Frank J. Accurso, MD, Children's Hospital Colorado, Aurora, CO; Karen S. McCoy, MD, Nationwide Children's Hospital, Columbus, OH; Joanne L. Billings, MD, University of Minnesota, Minneapolis, MN; Jeffrey J. Atkinson, MD, Washington University School of Medicine, St. Louis, MO; Theodore G. Liou, MD, University of Utah Health Sciences Center, Salt Lake City, UT; John P. Clancy, MD, University of Alabama, Birmingham, AL; Joseph M. Pilewski, MD, Children's Hospital of Pittsburgh, Pittsburgh, PA; James D. Acton, MD, Cincinnati Children's Hospital, Cincinnati, OH; Jane L. Burns, MD, Seattle Children's Hospital, Seattle, WA.
Anti-PcrV antibody in cystic fibrosis: A novel approach targeting Pseudomonas aeruginosa airway infection
Article first published online: 9 SEP 2013
© 2013 Wiley Periodicals, Inc.
Volume 49, Issue 7, pages 650–658, July 2014
How to Cite
Milla, C. E., Chmiel, J. F., Accurso, F. J., VanDevanter, D. R., Konstan, M. W., Yarranton, G., Geller, D. E. and for the KB001 Study Group (2014), Anti-PcrV antibody in cystic fibrosis: A novel approach targeting Pseudomonas aeruginosa airway infection. Pediatr. Pulmonol., 49: 650–658. doi: 10.1002/ppul.22890
Conflict of interest: None.
- Issue published online: 24 JUN 2014
- Article first published online: 9 SEP 2013
- Manuscript Accepted: 17 JUL 2013
- Manuscript Received: 21 FEB 2013
- KaloBios Pharmaceuticals, Inc., CFTDN
- cystic fibrosis;
- Pseudomonas aeruginosa;
- type III secretion system;
Pseudomonas aeruginosa (Pa) airway infection is associated with increased morbidity and mortality in cystic fibrosis (CF). The type III secretion system is one of the factors responsible for the increased virulence and pro-inflammatory effects of Pa. KB001 is a PEGylated, recombinant, anti-Pseudomonas-PcrV antibody Fab′ fragment that blocks the function of Pa TTSS. We studied the safety, pharmacokinetic (PK), and pharmacodynamic properties of KB001 in CF subjects with chronic Pa infection. Twenty-seven eligible CF subjects (≥12 years of age, FEV1 ≥40% of predicted, and sputum Pa density >105 CFU/g) received a single intravenous dose of KB001 (3 mg/kg or 10 mg/kg) or placebo. Safety, PK, Pa density, clinical outcomes, and inflammatory markers were assessed. KB001 had an acceptable safety profile and a mean serum half-life of 11.9 days. All subjects had Pa TTSS expression in sputum. There were no significant differences between KB001 and placebo for changes in Pa density, symptoms, or spirometry after a single dose. However, compared to baseline, at Day 28 there was a trend towards a dose-dependent reduction in sputum myeloperoxidase, IL-1, and IL-8, and there were significant overall differences in change in sputum neutrophil elastase and neutrophil counts favoring the KB001 10 mg/kg group versus placebo (−0.61 log10 and −0.63 log10, respectively; P < 0.05). These results support targeting Pa TTSS with KB001 as a nonantibiotic strategy to reduce airway inflammation and damage in CF patients with chronic Pa infection. Repeat-dosing studies are necessary to evaluate the durability of the anti-inflammatory effects and how that may translate into clinical benefit. (NCT00638365) Pediatr Pulmonol. 2014; 49:650–658. © 2013 Wiley Periodicals, Inc.