title: The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma.
abstract: BACKGROUND
  Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a TH1-mediated protective response.
  
  
  OBJECTIVE
  We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma.
  
  
  METHODS
  In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734).
  
  
  RESULTS
  All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n = 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n = 30, P < .05). At week 12, two thirds of the QbG10-treated patients had their asthma "well controlled" (Asthma Control Questionnaire score ≤0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration.
  
  
  CONCLUSIONS
  Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids.
authors: Insaf Respiratory Research Institute, Biebricher Allee 34, Wiesbaden, Germany.
authors: Kai-Michael
authors: KM
authors: Beeh
authors: Frank
authors: F
authors: Kanniess
authors: Frank
authors: F
authors: Wagner
authors: Cordula
authors: C
authors: Schilder
authors: Ingomar
authors: I
authors: Naudts
authors: Anya
authors: A
authors: Hammann-Haenni
authors: Joerg
authors: J
authors: Willers
authors: Hans
authors: H
authors: Stocker
authors: Philipp
authors: P
authors: Mueller
authors: Martin F
authors: MF
authors: Bachmann
authors: Wolfgang A
authors: WA
authors: Renner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; C559986:CYT003-QbG10; D005938:Glucocorticoids; D009841:Oligonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D009569:Nitric Oxide; D007073:Immunoglobulin E; D001507:Beclomethasone