title: A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease.
abstract: OBJECTIVE
  Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn's disease (CD).
  
  
  METHODS
  A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn's Disease Activity Index (CDAI) 250-400). Placebo was administered for 3 days; 60 mg semapimod intravenously for 1 day with placebo for 2 days; or 60 mg semapimod intravenously for 3 days. Participants who completed CD04 could participate in the open-label extension study, CD05, to receive up to five additional semapimod HCl 60 mg daily doses three times every 6-8 weeks. The main outcome measures were CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Endoscopic Inflammation Score (CDEIS) and serum C-reactive protein (CRP) concentration.
  
  
  RESULTS
  152 patients were randomised in CD04. Responses for 1 and 3 day regimens were similar to placebo for CDAI (p=0.82), IBDQ (p=0.85), CDEIS (p=0.57) and CRP (p=0.40). The only noteworthy treatment-related safety finding was infusion reaction (phlebitis): 7.3, 34.8 and 62.7% for the placebo and 1 and 3 day semapimod treatment groups, respectively (p<0.001). In the open-label CD05 study (included=119 patients) a posthoc analysis showed that the mean CDAI improved in patients receiving 6 compared with < or = 3 cumulative doses (204.1+/-83 vs 251.4+/-103.05, p=0.006).
  
  
  CONCLUSIONS
  Single and 3 day dosing of semapimod (< or = 180 mg) was ineffective for the treatment of moderate to severe CD. However, cumulative dosing > or = 360 mg was associated with decreased CDAI in a limited number of patients.
authors.affiliation: IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, 64239, Israel. irisd@tasmc.health.gov.il
authors.forename: Iris
authors.initials: I
authors.lastname: Dotan
authors.forename: Daniel
authors.initials: D
authors.lastname: Rachmilewitz
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
authors.forename: Asher
authors.initials: A
authors.lastname: Kornbluth
authors.forename: Alan L
authors.initials: AL
authors.lastname: Buchman
authors.forename: Shimon
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: Bernd
authors.initials: B
authors.lastname: Bokemeyer
authors.forename: Eran
authors.initials: E
authors.lastname: Goldin
authors.forename: Christian
authors.initials: C
authors.lastname: Maaser
authors.forename: Uma
authors.initials: U
authors.lastname: Mahadevan
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Hoffman
authors.forename: Douglas
authors.initials: D
authors.lastname: Homoky
authors.forename: Terry
authors.initials: T
authors.lastname: Plasse
authors.forename: Barbara
authors.initials: B
authors.lastname: Powers
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Daniel
authors.initials: D
authors.lastname: Hommes
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult; D000813:Anilides; D006146:Guanidines
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002097:C-Reactive Protein; D005765:Gastrointestinal Agents; D006835:Hydrazones; D007166:Immunosuppressive Agents; C097256:semapimod; D000813:Anilides; D006146:Guanidines