CNI-1493 for Treatment of Moderate to Severe Crohn’s Disease

Overview

The purpose of this study is to determine whether CNI-1493 is safe and effective in the treatment of moderate to severe Crohn's Disease.

Full Title of Study: “A Randomized, Double-Blind, Placebo-controlled Study of CNI-1493 for Treatment of Moderate to Severe Crohn’s Disease”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 2003

Detailed Description

Crohn's disease (CD) is a chronic inflammatory disease involving the upper and lower gastrointestinal tract and characterized by abdominal pain, weight loss, gastrointestinal bleeding and formation of fistulas between loops of bowel and from the bowel to the skin or other organs. Current therapy for active Crohn's disease consists of symptomatic treatment, nutritional therapy, salicylates and immunosuppressants or surgical management.

Tumor necrosis factor a (TNF-a) plays a central role in the initiation and amplification of the granulomatous inflammatory reaction seen in CD (van Deventer, 1997). Increased TNF-a is present in gut mucosa as well as in stool of patients with active CD (Braegger et al, 1992). CNI-1493 is a synthetic guanylhydrazone compound that is an inhibitor of TNF-a synthesis. A monoclonal antibody to TNF, infliximab, is now approved for treatment of CD, but not all patients respond and many who do respond eventually become refractory to this treatment as well.

CNI-1493 is a synthetic compound which blocks the production of several inflammatory cytokines, including TNF. Because it blocks production of multiple inflammatory mediators, it may be more active than products targeted to a specific cytokine. In addition, as it is not a biologic, it should not cause hypersensitivity reactions or induce formation of antibodies.

The purpose of this trial is to determine if CNI-1493 is safe and effective in treating patients with moderate to severe Crohn's Disease in a placebo controlled setting.

Interventions

  • Drug: semapimod
    • semapipmod 60 mg IV x 5 days
  • Drug: semapimod
    • IV 30 mg x 5 days
  • Drug: placebo
    • placebo IV

Arms, Groups and Cohorts

  • Experimental: Semapimod 60 mg
    • Semapimod 60 mg IV x 5 days
  • Experimental: Semapimod IV 30 mg
    • Semapimod IV 30 mg x 5 days
  • Placebo Comparator: Placebo
    • Placebo IV x 3 or 5 days

Clinical Trial Outcome Measures

Primary Measures

  • Change in CDAI
    • Time Frame: Day 29

Secondary Measures

  • Change in IBDQ
    • Time Frame: Day 29

Participating in This Clinical Trial

Inclusion Criteria

  • Baseline Crohn's Disease Activity Index (CDAI) 250-400, inclusive
  • Crohn's disease of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed by radiography and/or endoscopy
  • Patients receiving medications for CD must be on stable doses entering the study
  • Any CD medication which has been discontinued must have been discontinued at least 4 weeks prior to screening, with the exception of infliximab, which must have been discontinued at least 8 weeks prior to screening

Exclusion Criteria

  • Patients with any ostomy or extensive bowel resection
  • Current evidence of bowel obstruction or history within the preceding six months as confirmed by radiography, endoscopy, or surgery
  • Patients with stool examination positive for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin
  • Treatment with any other experimental therapeutics within the last 4 weeks before enrollment

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ferring Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Daan Hommes, M, Principal Investigator, Academic Medical Center, Netherlands

References

Hommes D, van den Blink B, Plasse T, Bartelsman J, Xu C, Macpherson B, Tytgat G, Peppelenbosch M, Van Deventer S. Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. Gastroenterology. 2002 Jan;122(1):7-14.

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