Cimzia Versus Cimzia Plus Azathioprine in the Treatment of Active Crohn's Disease

Inclusion Criteria:

1. The patient has signed an Informed Consent Form (ICF).

2. The patient is ambulatory, community-dwelling male or non-pregnant female and is aged
between 18 and 70 years at the Screening Visit. Lactating females must agree not to
breastfeed.

3. Sexually active female patients of childbearing potential must agree to use one of
the following methods of birth control from the date they sign the ICF until the
conclusion of the trial:

a. Hormonal contraception (i.e. oral contraceptive, contraceptive implant, or
injectable hormonal contraceptive) b. Double-barrier birth control (e.g. condom plus
intrauterine device, diaphragm plus spermicide) c. Surgical sterilization (i.e.
bilateral oophorectomy, hysterectomy, or tubal ligation) d. Maintenance if a
monogamous relationship with a male partner who has been surgically sterilized by
vasectomy

4. Females of childbearing potential must have a negative serum pregnancy test at the
Randomization Visit (first study treatment visit) prior to dosing.

5. Patient has no clinically significant findings on a physical examination, 12-lead
electrocardiogram (ECG) and clinical laboratory tests (clinical chemistry panel,
complete blood count [CBC], urinalysis [UA]) after signing the ICF but before
receiving the first dose of study drug. (Note: The Investigator will determine if a
particular finding is clinically significant. In making this determination, the
investigator will consider whether the particular finding could prevent the patient
from performing any of the protocol-specified assessments, could represent a
condition that would exclude the patient from the trial, could represent a safety
concern if the patient participates in the trial, or could confound the
trial-specified assessments of safety or efficacy.)

6. Patient is fluent in English.

7. Are considered eligible according to the following TB screening criteria:

• Have no history of latent or active TB prior to screening. An exception is made for
patients with a history of latent TB and documentation of having completed
appropriate treatment for latent TB within 3 years prior to the first administration
of study agent. Appropriate documentation to verify that there had been treatment
with a antituberculous treatment must be established prior to study participation.

• Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.

• Have no recent close contact with a person with active TB.

• Subject has a negative purified protein derivative test within 30 days prior to the
first dose. Tuberculin skin tests should be considered positive when they have
greater than or equal to 5 mm of induration at 48 to 72 hours after test is placed.
Subjects with a positive tuberculin skin test (if less than or equal to 14 mm of
induration) are allowed if they have a history of Bacillus Calmette-Guerin
vaccination with a negative Quantiferon test in the past year, no symptoms per
tuberculosis workup, and a negative chest X-ray.

8. Be able to adhere to the required study visit schedule and comply with noted protocol
requirements.

9. Subject has established ileal, ileo-colonic, or colonic Crohn's disease for a minimum
of 3 months.

10. Subject has moderately to severely active Crohn's disease, as defined by a Crohn's
Disease Activity Index (CDAI) score from 225 to 450 at screening and baseline and
must also have an SES score that falls under the auspice of moderate to moderately
severe disease (10-15).

11. Subject has evidence of active inflammation, as demonstrated by any of the following:

- Elevated C reactive protein (CRP) at screening (>2.87 mg/L, or upper limit of
normal (ULN) as set by local laboratory)

- Endoscopic evidence of inflammation during the screening period or within 8
weeks prior to the screening period

12. Subjects are allowed to continue on concurrent treatment with the following agents:

- 5-aminosalicylates, if stable dosage for at least 2 weeks prior to screening
(same dosage to be maintained throughout the trial)

- Probiotics, provided that the dose has been stable for the 2 weeks prior to
enrollment

- Antidiarrheals (eg, loperamide, Imodium) for control of chronic diarrhea; as per
standard CDAI protocols, the use of antidiarrheals will be assessed at each
visit.

Additional eligibility information

SES-CD The subject has a diagnosis of active moderate to severe CD at screening with these
specific findings: the presence of large ulcerations (0.5cm is the minimal diameter in
size to be categorized as large - this also constitutes between 2-3 points on the SES-CD
score), the extent of ulcerated surface (the minimal percentage has got to be at least 10%
- this also constitutes between 2-3 points on the SES-CD score), the extent of the
affected surface (50% is the minimal percentage to fall in the moderate category - would
constitute between 2-3 points on the SES-CD score) and finally the presence and type of
narrowing found (number of strictures found and if the colonoscope can be passed or cannot
be passed - this also constitutes between 2-3 points on the SES-CD score). The minimal
score will be between 10 and 15. The local endoscopist (investigator) will determine
whether subjects meet the entrance criteria from the SES scoring perspective. An appendix
will be attached to define in a table the simple endoscopic scoring for Crohn's Disease
(Appendix 1).

CDAI Crohn's Disease Activity Index scoring: this consists of eight variables including
five subject reported outcomes. Variables 1,2,3,4 and 5 will be obtained from the
patient's diary (see table 2a, subject diary, under Appendix 2, Crohn's Disease Activity
Index Variables) completed by the patient during the 7 days prior to each CDAI evaluation.
The Standard Height and Weight Table (Table 2b) must be used to calculate variable 8. The
score from each variable is weighted by applying the multiplier shown. The total CDAI
score is then determined by calculating the sum of the individual, weighted scores. A
minimum score of 225 points is required and cannot exceed 450. These are the two primary
criteria for entry that have to do with the study outcomes proposed.

Exclusion Criteria:

1. The patient has any condition, including clinically significant abnormalities on
Screening laboratory test and/or medical history found during Screening assessments,
or any acute or chronic condition, that, in the opinion of the investigator,
constitutes a risk for the patient or a contraindication for participation in and
completion of the study, or could interfere with study objectives, conduct, or
evaluations (such as unstable diabetes mellitus, thyroid disease, vascular disease,
end-stage coronary disease, pulmonary disease, liver disease, renal disease and any
metabolic disorders that are also uncontrolled).

2. The patient has major surgery scheduled during the study period.

3. The patient has a history of cancer, except for adequately treated basal cell
carcinoma of the skin, cervical dysplasia, or carcinoma in situ of the skin or the
cervix.

4. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or
for a 6-month period thereafter.

5. Have shown a previous immediate hypersensitivity response, including anaphylaxis, to
an immunoglobulin product (plasma-derived or recombinant, e.g. monoclonal antibody).

6. Have received within 3 months prior to screening or are expected to receive any live
viral (e.g. small-pox) or live bacterial vaccinations during the trial or up to 3
months after the last administration of study agent.

7. Have evidence of an active infection at the time of randomization or have had a
serious infection not related to CD (e.g., hepatitis, pneumonia, or pyelonephritis),
within 6 months prior to screening.

8. Have or have had an opportunistic infection (e.g., herpes zoster [shingles],
cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria
other than TB) within 6 months prior to screening. Have current active hepatitis B
(including chronic active hepatitis B or asymptomatic carrier state [hepatitis B
surface antigen positive; HBsAg-positive]) or a history of hepatitis C infection.

9. Chronic pancreatitis.

10. Have any condition that, in the opinion of the investigator, would compromise the
well-being of the patient or the study or prevent the patient from meeting or
performing study requirements.

11. Have multiple sclerosis or other central demyelinating disorder.

12. Have a history of lymphoproliferative disease including lymphoma, or signs and
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy
of unusual size or location (e.g., nodes in the posterior triangle of the neck,
intraclavicular, epitrochlear, or periaortic areas), or splenomegaly.

13. Have a transplanted organ (with the exception of a corneal transplant performed > 3
months prior to screening).

14. Have documented or suspected human immunodeficiency virus (HIV) infection.

15. Evidence of abdominal abscess at the initial screening visit

16. Extensive colonic resection, subtotal or total colectomy

17. History of >3 small bowel resections or diagnosis of short bowel syndrome

18. Have received tube feeding, defined formula diets, or parenteral alimentation within
21 days prior to the administration of the first dose of study drug

19. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine

20. Within 30 days prior to enrollment, have received any of the following for the
treatment of underlying disease:

- Non-biologic therapies (e.g., cyclosporine, thalidomide)

- A non-biologic investigational therapy

- An approved non-biologic therapy in an investigational protocol

20. Within 60 days prior to enrollment, have received any of the following:

- Infliximab

- Certolizumab pegol

- Adalimumab

- Any other investigational or approved biological agent, other than local injections
for non inflammatory bowel disease (IBD) conditions (e.g. intraocular-injections for
the treatment of wet macular degeneration) 21. Any prior exposure to natalizumab,
efalizumab, or rituximab 22. Evidence of or treatment for C. difficile infection or
other intestinal pathogen within 28 days prior to enrollment 23. Have a history of
substance abuse (drug or alcohol) within the previous 3 years, history of
noncompliance to medical regimens, or other condition/circumstance that could
interfere with the patient's adherence to protocol requirements (e.g., psychiatric
disease, lack of motivation, travel, etc).

24. Have Ulcerative Colitis as their diagnosis 25. Are employees of the investigator
or study center, with direct involvement in the proposed study or other studies under
the direction of that investigator or study center, as well as family members of the
employees or the investigator.