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

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.