title: A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn's disease.
abstract: CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn's medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a ≥ 70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p = .667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p = .833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p = .111). At week 12, response rates were 47%, 56% (OR = 1.44; p = .168), 49% (OR = 1.07; p = .792), and 61% (OR = 1.74; p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p = .629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00306215.
authors.affiliation: John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Satish
authors.initials: S
authors.lastname: Keshav
authors.forename: Tomáš
authors.initials: T
authors.lastname: Vaňásek
authors.forename: Yaron
authors.initials: Y
authors.lastname: Niv
authors.forename: Robert
authors.initials: R
authors.lastname: Petryka
authors.forename: Stephanie
authors.initials: S
authors.lastname: Howaldt
authors.forename: Mauro
authors.initials: M
authors.lastname: Bafutto
authors.forename: István
authors.initials: I
authors.lastname: Rácz
authors.forename: David
authors.initials: D
authors.lastname: Hetzel
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.forename: Per
authors.initials: P
authors.lastname: Karlén
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schall
authors.forename: Pirow
authors.initials: P
authors.lastname: Bekker
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003424:Crohn Disease / Q000188:drug therapy*; D016099:Endoscopy, Gastrointestinal; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D006801:Humans; D007422:Intestines / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D054388:Receptors, CCR / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C119309:CC chemokine receptor 9; C583420:CCX282-B; D054388:Receptors, CCR; D013449:Sulfonamides; D002097:C-Reactive Protein