title: A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease.
abstract: BACKGROUND
  Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease.
  
  
  METHODS
  We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity.
  
  
  RESULTS
  STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15%) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%).
  
  
  CONCLUSIONS
  Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.
authors.affiliation: Brigham & Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Burakoff
authors.forename: Charles F
authors.initials: CF
authors.lastname: Barish
authors.forename: Dennis
authors.initials: D
authors.lastname: Riff
authors.forename: Ronald
authors.initials: R
authors.lastname: Pruitt
authors.forename: William Y
authors.initials: WY
authors.lastname: Chey
authors.forename: Francis A
authors.initials: FA
authors.lastname: Farraye
authors.forename: Ira
authors.initials: I
authors.lastname: Shafran
authors.forename: Seymour
authors.initials: S
authors.lastname: Katz
authors.forename: Charles L
authors.initials: CL
authors.lastname: Krone
authors.forename: Martha
authors.initials: M
authors.lastname: Vander Vliet
authors.forename: Christopher
authors.initials: C
authors.lastname: Stevens
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Sherman
authors.forename: Eric
authors.initials: E
authors.lastname: Jacobson
authors.forename: Ronald
authors.initials: R
authors.lastname: Bleday
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D006835:Hydrazones; D018664:Interleukin-12 / Q000037:antagonists & inhibitors*; D053759:Interleukin-23 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines; D012074:Remission Induction; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D006835:Hydrazones; D053759:Interleukin-23; D009025:Morpholines; D011743:Pyrimidines; D014227:Triazines; D018664:Interleukin-12; C504227:apilimod