title: Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease.
abstract: BACKGROUND
  Many patients with active Crohn's disease do not adequately respond to therapies, highlighting the need for new treatments.
  
  
  OBJECTIVE
  To conduct a randomised, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of vercirnon, an oral inhibitor of CC chemokine receptor-9, for the treatment of patients with moderately-to-severely active Crohn's disease.
  
  
  METHODS
  Patients with a Crohn's Disease Activity Index (CDAI) of 220-450, plus evidence of active disease (endoscopically confirmed or elevation of both C-reactive protein and faecal calprotectin), who had failed corticosteroid or immunosuppressant therapy were enrolled. Patients were equally randomised to receive placebo, vercirnon 500 mg once daily or vercirnon 500 mg twice daily. The primary endpoint was clinical response, defined as a 100-point decrease in CDAI from baseline to week 12.
  
  
  RESULTS
  Six hundred and eight patients were randomised. Patient characteristics and baseline demographics were similar among the groups. The proportions of patients achieving a clinical response were 25.1%, 27.6% and 27.2% for placebo, once daily and twice daily respectively; treatment differences were not significant (2.5%; 95% confidence interval, CI -6.1% to 11.0%, P = 0.546 for once daily vs. placebo, and 2.1%; 95% CI -6.5% to 10.7%, P = 0.648 for twice daily vs. placebo). Adverse events were reported in 69.8%, 73.3% and 78.1% with serious adverse events in 8.9%, 5.9%, and 6.0% of patients in the placebo, once-daily and twice-daily groups, respectively.
  
  
  CONCLUSIONS
  We did not demonstrate efficacy of vercirnon as an induction therapy in patients with moderately-to-severely active Crohn's disease; its effect in maintenance therapy was not addressed.
authors.affiliation: Robarts Clinical Trials Inc, Robarts Research Institute, Western University, London, ON, Canada.
authors.forename: B G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Hopital Saint-Louis, APHP, Université Paris Diderot, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Allez
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
authors.forename: R N
authors.initials: RN
authors.lastname: Fedorak
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Seidler
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Fiona Stanley Hospital, Murdoch, WA, Australia.|Centre for inflammatory Bowel Diseases, Saint John of God Hospital, Subiaco, WA, Australia.
authors.forename: I C
authors.initials: IC
authors.lastname: Lawrance
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, Research Triangle Park, NC, Philadelphia, PA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Maroney
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, Research Triangle Park, NC, Philadelphia, PA, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Jurgensen
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, Research Triangle Park, NC, Philadelphia, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Heath
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, Research Triangle Park, NC, Philadelphia, PA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Chang
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005243:Feces; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054388:Receptors, CCR / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: C119309:CC chemokine receptor 9; C583420:CCX282-B; D039841:Leukocyte L1 Antigen Complex; D054388:Receptors, CCR; D013449:Sulfonamides; D002097:C-Reactive Protein