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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Double-Blind, Placebo-controlled Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: semapimod
* Drug: semapimod
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semapimod 60 mg<br>Semapimod 60 mg IV x 5 days | Drug: semapimod<br>* semapipmod 60 mg IV x 5 days<br>* Other names: CNI-1493;|
| Experimental: Semapimod IV 30 mg<br>Semapimod IV 30 mg x 5 days | Drug: semapimod<br>* IV 30 mg x 5 days<br>* Other names: CNI-1493;|
| Placebo Comparator: Placebo<br>Placebo IV x 3 or 5 days | Drug: placebo<br>* placebo IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CDAI |  | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IBDQ |  | Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease