title: Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study.
abstract: BACKGROUND
  Allergic symptoms are generally caused by exposure to substances to which people have become sensitized. Associated with this is an 'unbalanced' Th1/Th2 immune response with T cell responses skewed towards the production of Th2 cytokines, IL-4, 5, and 13 and high levels of IgE antibodies. Current immune modulating therapies require the use of allergens, carrying the risk to induce potentially severe allergic reactions.
  
  
  OBJECTIVE
  Goal of the present study was to assess the safety and efficacy of an allergen-free immune modulator in patients suffering from perennial allergy.
  
  
  METHODS
  In order to be protected from immediate degradation upon injection, a toll-like receptor 9 (TLR9) agonist was packaged into virus-like particles. These nanoparticles loaded with TLR9 ligands (CYT003-QbG10) were injected six times, at weekly intervals, into patients with house dust mite allergy in an attempt to ameliorate allergic symptoms by modifying the immune response towards allergens. Two different doses were compared against placebo in this double-blind, randomized phase IIb study (n=299). Public trial registry: http://clinicaltrials.gov (NCT00800332).
  
  
  RESULTS
  The treatment was safe and generally well tolerated. Rhinoconjunctivitis symptoms were significantly lower in patients treated with high dose of CYT003-QbG10 as compared with placebo (scores 0.31 vs. 0.52, P=0.04) based on a standardized average combined symptom and medication score. Furthermore, patients in the high dose group reported a significantly better quality of life score post-treatment than patients on placebo (scores 0.71 vs. 1.21, P=0.02). The conjunctival provocation test revealed a median 10-fold increase in allergen tolerance in the high dose group while in the placebo group it remained unchanged.
  
  
  CONCLUSIONS
  Treatment with high-dose CYT003-QbG10 improved disease symptoms and reduced medication use in allergic individuals thus providing first evidence for a new potential immunotherapeutic.
authors.affiliation: Zentrum fuer Rhinologie & Allergologie, Wiesbaden, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Klimek
authors.forename: J
authors.initials: J
authors.lastname: Willers
authors.forename: A
authors.initials: A
authors.lastname: Hammann-Haenni
authors.forename: O
authors.initials: O
authors.lastname: Pfaar
authors.forename: H
authors.initials: H
authors.lastname: Stocker
authors.forename: P
authors.initials: P
authors.lastname: Mueller
authors.forename: W A
authors.initials: WA
authors.lastname: Renner
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000628:therapy*; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D011788:Quality of Life; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000628:therapy*; D011795:Surveys and Questionnaires; D051217:Toll-Like Receptor 9 / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C559986:CYT003-QbG10; D009841:Oligonucleotides; D051217:Toll-Like Receptor 9