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Anti-PcrV antibody in cystic fibrosis: a novel approach targeting Pseudomonas
aeruginosa airway infection
#MMPMID24019259
Milla CE
; Chmiel JF
; Accurso FJ
; VanDevanter DR
; Konstan MW
; Yarranton G
; Geller DE
Pediatr Pulmonol
2014[Jul]; 49
(7
): 650-8
PMID24019259
show ga
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?
|Adult
[MESH]
|Anti-Bacterial Agents/pharmacokinetics/pharmacology/*therapeutic use
[MESH]
|Antibodies, Bacterial/pharmacology/*therapeutic use
[MESH]
|Antibodies, Monoclonal/pharmacokinetics/pharmacology/*therapeutic use
[MESH]
|Biomarkers/metabolism
[MESH]
|Chronic Disease
[MESH]
|Cystic Fibrosis/*complications
[MESH]
|Double-Blind Method
[MESH]
|Drug Administration Schedule
[MESH]
|Female
[MESH]
|Follow-Up Studies
[MESH]
|Half-Life
[MESH]
|Humans
[MESH]
|Immunoglobulin Fab Fragments/pharmacology/*therapeutic use
[MESH]
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