title: CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study.
abstract: BACKGROUND
  New treatment options are required for patients with asthma not sufficiently controlled with inhaled therapies. In a Phase 2a trial, CYT003, a Toll-like receptor-9 agonist immunomodulator, improved asthma control during inhaled glucocorticosteroid reduction in patients with allergic asthma. This double-blind Phase 2b study assessed the efficacy and safety of CYT003 in patients with persistent moderate-to-severe allergic asthma not sufficiently controlled on standard inhaled glucocorticosteroid therapy with/without long-acting beta-agonists (LABAs).
  
  
  METHODS
  Overall, 365 patients received seven doses of subcutaneous CYT003 (0.3, 1, or 2 mg) or placebo as add-on therapy to conventional controller medication. Change from baseline in Asthma Control Questionnaire (ACQ) score was the primary outcome; secondary outcomes included change in forced expiratory volume, Mini Asthma Quality of Life Questionnaire, and safety.
  
  
  RESULTS
  All groups, including placebo, showed a clinically important improvement in ACQ score; however, there was no significant difference between the CYT003 and placebo groups at week 12 (least-squares mean difference 0.3 mg: -0.027 [95% confidence interval -0.259 to 0.204]; 1 mg: 0.097 [-0.131 to 0.325]; 2 mg: 0.081 [-0.148 to 0.315]). No significant differences were seen in secondary outcomes. CYT003 was well tolerated; the most common treatment-emergent adverse events were injection site reactions. Due to lack of efficacy, the study was prematurely terminated at the end of the treatment phase with no further follow-up.
  
  
  CONCLUSIONS
  Toll-like receptor-9 agonism with CYT003 showed no additional benefit in patients with insufficiently controlled moderate-to-severe allergic asthma receiving standard inhaled glucocorticosteroid therapy with or without LABAs.
authors.affiliation: Department of Internal Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Casale
authors.affiliation: IPS Research Company, Oklahoma City, OK, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cole
authors.affiliation: Medical Department, Institut fuer Gesundheitsfoerderung, Ruedersdorf Brandenburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Beck
authors.affiliation: Department of Pneumology, University of Marburg, Marburg, Germany.
authors.forename: C F
authors.initials: CF
authors.lastname: Vogelmeier
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Willers
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Lassen
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Hammann-Haenni
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Trokan
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Saudan
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Wechsler
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: C559986:CYT003-QbG10; D007155:Immunologic Factors; D009841:Oligonucleotides; D051217:Toll-Like Receptor 9
keywords: Asthma Control Questionnaire; CpG-motifs; TLR-9 agonist; asthma; immunotherapeutic