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A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease
  1. Iris Dotan1,
  2. Daniel Rachmilewitz2,
  3. Stefan Schreiber3,
  4. Rami Eliakim4,
  5. C Janneke van der Woude5,
  6. Asher Kornbluth6,
  7. Alan L Buchman7,
  8. Shimon Bar-Meir8,
  9. Bernd Bokemeyer9,
  10. Eran Goldin10,
  11. Christian Maaser11,
  12. Uma Mahadevan12,
  13. Ursula Seidler13,
  14. Jörg C Hoffman14,
  15. Douglas Homoky15,
  16. Terry Plasse16,
  17. Barbara Powers16,
  18. Paul Rutgeerts17,
  19. Daniel Hommes18 on behalf of the Semapimod-CD04/CD05 Investigators
  1. 1IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
  2. 2Shaare Zedek Hospital, Jerusalem, Israel
  3. 3University of Kiel, Kiel, Germany
  4. 4Rambam Health Care Campus, Haifa, Israel
  5. 5Erasmus Medical Center, Rotterdam, The Netherlands
  6. 6The Henry D Janowitz Division of Gastroenterology, The Mount Sinai Medical Center, New York, USA
  7. 7Division of Gastroenterology and IBD Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
  8. 8Chaim Sheba Medical Center, Tel Hashomer, Israel
  9. 9Gastroenterologische Fachpraxis, Minden, Germany
  10. 10Hadassah Medical Center, Jerusalem, Israel
  11. 11University of Münster, Münster, Germany
  12. 12University of California, San Francisco, California, USA
  13. 13Medizinischen Hochschule-Hannover, Hannover, Germany
  14. 14Charité, Campus Benjamin Franklin, Berlin, Germany
  15. 15Gastroenterology Associates, Kingsport Tennessee, USA
  16. 16Cytokine PharmaSciences, Inc., King of Prussia, Pennsylvania, USA
  17. 17Academic Hospital Gasthuisberg, Leuven, Belgium
  18. 18Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Iris Dotan, IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, 64239, Israel; irisd{at}tasmc.health.gov.il

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 ≤3 cumulative doses (204.1±83 vs 251.4±103.05, p=0.006).

Conclusions Single and 3 day dosing of semapimod (≤180 mg) was ineffective for the treatment of moderate to severe CD. However, cumulative dosing ≥360 mg was associated with decreased CDAI in a limited number of patients.

  • Clinical trials
  • CNI-1493
  • Crohn's disease
  • MAPK inhibitor
  • semapimod
  • TNFα

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Footnotes

  • Funding The CD04 and CD05 studies were funded by Cytokine PharmaSciences.

  • Competing interests Dan Hommes has received funding from Cytokine Pharmasciences, Inc. as a consultant for the semapimod program. Terry Plasse was an employee of Cytokine Pharmasciences, Inc. at the time the study was conducted. Barbara Powers is Vice President of Clinical Development for Cytokine Pharmasciences, Inc., the study sponsor.

  • Patient consent Obtained.

  • Ethics approval The local Investigational Review Board or Ethics Committee at each site apporved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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