Clinical trial NCT00038766: CNI-1493 for Treatment of Moderate to Severe Crohn's Disease
Official title: A Randomized, Double-Blind, Placebo-controlled Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn Disease
Keywords: Inflammatory Bowel Disease
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2002-06-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in CDAI
timeFrame: Day 29
Secondary outcomes:
measure: Change in IBDQ
timeFrame: Day 29
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Institute of Healthcare Assessment
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Charlotte
country: United States
facility: Charlotte Gastroenterology and Hepatology, PLLC
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Research
state: Oklahoma
city: Lancaster
country: United States
facility: Regional Gastroenterology Associates of Lancaster, Ltd.
state: Pennsylvania
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
Study officials:
affiliation: Academic Medical Center, Netherlands
name: Daan Hommes, M
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1053/gast.2002.30770.