Imuran Dosing in Crohn's Disease Study

This multi-center, double blind (patients and doctors do not know treatment group
assignment), randomized (patients are put in 1 of 2 groups) clinical trial which will compare
two 52-week-long azathioprine(AZA) dosing methods.

The patients enrolled will all be taking steroids (prednisone or budesonide)or have just been
prescribed a steroid. The patients will be either in remission on steroids, but cannot taper
off without a flare, patients who are on steroids and are still having Crohn's symptoms, or
patients who need to start taking steroids.

After a two week screening period, patients fitting enrollment criteria will be begin taking
study drug. Patients will begin to taper steroids per a set schedule, and taper off steroids
completely by week 13. Patients who need to go back on steroids because of returned symptoms
are allowed to, per a set schedule in the protocol. Patients will have monthly visits that
include physical exams, blood tests and a quality of life questionnaire. Patients will be
required to keep a diary of abdominal pain, liquid or soft stools and general well being.

After 6 months, only patients in remission (patients not on steroids, and not having active
symptoms) will be allowed to continue for last 6 months of the study. Study visits during the
last 6 months will be every 2 months, and include physical exams and blood tests, and a
quality of life questionnaire.

Patients in the study may receive dose changes, and this will require additional blood tests
for safety.

Inclusion Criteria:

- 10-70 years-old., Weigh 20-100 kg (44-220 lbs).

- CD of the ileum, colon or ileocolon, verified by colonoscopy, barium enema, or small
bowel series performed within 36 months

- Perianal fistulae will be eligible provided that the perianal disease does not account
for the preponderance of symptoms.

- Have steroid-dependent, steroid-refractory or steroid naive CD.

- Steroid-dependent CD: CDAI or mCDAI of < 150 while receiving prednisone 10-40
mg/day or budesonide 3-9 mg/day for at least 12 weeks prior to screening, but
unable to taper prednisone below 10 mg/day or budesonide below 3 mg/day without
experiencing a flare within the previous 6 months. Steroids must be at a stable
dose for 2 weeks prior to screening (week #-2), prednisone at a dose of 10-40
mg/day and budesonide at a dose of 3-9 mg/day.

- Steroid-refractory CD: currently moderately active CD (CDAI or mCDAI 200 - 450)
despite treatment with 40 kg) or 0.5 mg/kg/day (if weighing 20 mg/day (if
weighing prednisone <40 9 mg/day for the previous 4 weeks prior to the screening
kg), or budesonide evaluation. Prednisone or budesonide must be at a stable dose
for 2 weeks prior to screening (week #-2).

- Steroid-naïve CD: currently moderately active CD, (CDAI or mCDAI 200 - 450) and
one of the following:

1. Despite treatment with aminosalicylates and/or antibiotics for the previous
4 weeks prior to the screening evaluation, who are candidates for prednisone
or budesonide.

2. Not currently on therapy, who are candidates for prednisone or budesonide

3. Patients with prior exposure to steroids, who have not been treated with
steroids for 4 weeks prior to screening, and are candidates for prednisone
or budesonide Prednisone or budesonide will be started at the screening
visit, at a dose of 40 mg/day or 9 mg/day and tapered per the steroid taper.

Patients who have started steroids up to 14 days prior to screening will also qualify as
steroid naïve, however patient needs to be on 40 mg prednisone or 9 mg budesonide.

- Discontinue oral or rectal 5-Aminosalicylic acid (5-ASA) therapies, rectal steroids,
ciprofloxacin or metronidazole at the screening visit.

Exclusion Criteria:

- CDAI > 450

- CD requiring hospitalization and intravenous (iv) corticosteroids, iv antibiotics or
total parenteral nutrition (TPN).

- TPN or enteral nutrition of >1000 Calories/day (both TPN and elemental diets impact
the CDAI).

- History of resection of more than 100 cm of small bowel, total proctocolectomy, or
subtotal colectomy with ileorectal anastomosis

- Ileostomy or colostomy

- Severe fixed symptomatic stenosis of the small or large intestine

- Blood transfusion within 3 months before screening

- Treatment with 6-MP or AZA within the 6 months prior to screening

- Immunosuppressants or biologics 3 months before screening

- Treatment 2 weeks before screening:

- Allopurinol;

- Trimethoprim-sulfamethoxazole;

- NSAIDs or aspirin >81mg/day;

- Cholestyramine or other drugs interfering with enterohepatic circulation;

- Furosemide and thiazide diuretics;

- Fish-oil preparations.

- Discontinue use at screening: Oral or rectal 5-ASA, rectal steroids, metronidazole or
quinolones

- Any prior treatment with natalizumab

- Presence of abnormal laboratory parameters:

- Carriage of hepatitis B surface antigen or positive hepatitis C antibody

- Lack of one acceptable form of contraception while receiving AZA

- Low TPMT activity