Alicaforsen (ISIS 2302) in Patients With Active Crohn’s Disease

ISIS 2302 is an antisense oligonucleotide drug that reduces the production of a specific protein called intercellular adhesion molecule (ICAM-1), a substance that plays a significant role in the increase of inflammation. People with Crohn’s disease have been shown to over-produce ICAM-1 in their gut tissues. Alicaforsen works by blocking ICAM-1 messenger RNA, the “instruction” molecule that is required for the production of ICAM-1 protein. This trial will examine effects of alicaforsen delivered by 2-hour intravenous infusion over a four-week period, compared to a placebo. Patients may remain on stable background 5-ASA, antibiotic, or immunosuppressive drugs, and prednisone (or equivalent) at </= 30 mg per day.

Inclusion Criteria

1. Age >/= 12 years
2. Weight >/= 36 kg
3. CDAI score of 220 – 400
4. Documentation of Crohn’s disease activity by endoscopy, biopsy or imaging in the last 2 years
5. No TNF-α inhibitor treatment for three months prior to first study drug infusion

Exclusion Criteria

1. Known severe, fixed, symptomatic stenosis of the small or large intestine with significant dilation
2. Extensive external fistulization (> 3 external fistulae which are expressible with gentle compression); colostomy or ileostomy
3. Active infection, including infectious colitis, or infection with HIV, Hepatitis B or Hepatitis C
4. Malignancy within 3 years or poorly controlled medical illness
5. Requires intravenous heparin therapy or with a history of a bleeding problem