Anti-PcrV antibody in cystic fibrosis: a novel approach targeting Pseudomonas aeruginosa airway infection.

ABSTRACT: 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 >10(5) ?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?log(10) and -0.63?log(10) , respectively; P?

SUBMITTER: Milla CE 

PROVIDER: S-EPMC4079258 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature