Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Double-blind Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Brief Summary: The objective of this study is to assess the efficacy and safety of adalimumab for the induction of clinical remission in subjects with moderately to severely active ulcerative colitis.


Options:
A: Inclusion Criteria:

* Patients must have had ulcerative colitis of at least 3 months' duration at screening, confirmed by the biopsy taken at screening
* Patients must have active colitis confirmed during the screening sigmoidoscopy
* Patients must have active disease.

Exclusion Criteria:

* Patient must not be likely to require surgical removal of all or part of the colon within 12 weeks of beginning the study
* Patient must not require, or required within the 2 months prior to beginning the study, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage
B: Inclusion Criteria:

1. Patients over age of 18 years who are capable of providing written informed consent.
2. Confirmed diagnosis of ulcerative colitis by conventional clinical, endoscopic and histological criteria.
3. Failure of response to at least two weeks of oral prednisolone 40mg/day.
4. Active colitis as assessed by a Mayo score \[21\] of 6-12 inclusive (see Appendix 1)

Exclusion Criteria:

1. Patients under 18 or unable to give informed consent.
2. Patients in their first attack of ulcerative colitis.
3. Patients with severe ulcerative colitis as defined by presence of any of: temperature \>37.5oC, pulse rate \>100, focal severe or rebound abdominal tenderness, haemoglobin \< 10.0g/dl, serum albumin \<3.5 g/dl, transverse colon diameter greater than 5.0cms on plain abdominal X ray.
4. Patients who are pregnant, post partum (\<3months) or breast feeding
5. Patients who are at risk of pregnancy and not using a reliable form of contraception (oral contraceptive and barrier or barrier plus spermicide).
6. Patients with a stoma
7. Positive stool culture for pathogens or test for C difficile at screening within 7 days prior to trial entry
8. Patients for whom a baseline Mayo score can not be reliably calculated: frequent use of laxatives (for proximal constipation) or antimotility agents (for control of diarrhoea)
9. Any change to maintenance medication for ulcerative colitis: azathioprine or 6-mercaptopurine within previous 3 months or 5-aminosalicylates within previous one month
10. Any change to rectal therapy for colitis within the previous two weeks.
11. Participation in other trials in the last 3 months.
12. Serious intercurrent infection or other clinically important active disease (including renal and hepatic disease)

    -
C: Inclusion Criteria:

* Participants diagnosed with moderately to severely active ulcerative colitis (UC) defined by a Mayo score of 6 to 12 inclusive at Baseline (Week 0), including an endoscopic (examination of an internal part of the body with a lighted tube; looking at a part of the body with a lighted tube) subscore of greater than or equal to 2
* Participants must have biopsy results (collected at the screening endoscopy (procedure or obtained within the last year) consistent with the diagnosis of UC
* Participants either currently receiving treatment with, or have a history of failure to respond to, or tolerate, at least 1 of the following therapies: oral 5-aminosalicylate, oral corticosteroids, 6-mercaptopurine and azathioprine
* Participants with current dependency or with a history of corticosteroid dependency (i.e., an inability to successfully taper corticosteroids without a return of the symptoms of UC)
* Not have a diagnosis of active tuberculosis
* Participants with negative stool test for enteric (by way of the intestines) pathogens

Exclusion Criteria:

* Participants with prior exposure to biologic anti-tumor necrosis factor (TNF) agents
* Participants with severe extensive UC that is likely to require a colectomy (surgery to remove part or all of the colon) within 12 weeks of study entry
* Participants having UC limited to the rectum only or to less than 20 centimeter of the colon
* Presence of a stoma (an artificial permanent opening especially in the abdominal wall made in surgical procedures) or presence of a fistula
* Participants with a history of extensive colonic resection
D: The following eligibility criteria applied to participants enrolled following Amendment 3 to the study protocol.

Inclusion Criteria:

1. Male and female participants \>= 18 years of age
2. Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline
3. Diagnosis of active ulcerative colitis confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of infection
4. Active UC with a Mayo score of 6 to 12 points and endoscopy subscore of 2 to 3 points, despite concurrent treatment with at least 1 of the following (oral corticosteroids or immunosuppressants or both as defined below):

   * Stable oral corticosteroid dose (prednisone dose of \>= 20 mg/day or equivalent) for at least 14 days prior to Baseline or stable oral corticosteroid dose (prednisone of \< 20 mg/day) for at least 40 days prior to Baseline.

   and/or
   * At least a consecutive 90 day course of azathioprine or 6-mercaptopurine (6 MP) prior to Baseline, with a dose of azathioprine \>= 1.5 mg/kg/day or 6 MP \>= 1 mg/kg/day (rounded to the nearest available tablet formulation), or a dose that is the highest tolerated by the participant (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time. Participant was to be on a stable dose for at least 28 days prior to Baseline.

   Concurrent therapy was not required for participants who were previously treated with corticosteroids or immunosuppressants (azathioprine or 6-MP) during the previous 5 years and, in the judgment of the investigator, have failed to respond to or could not tolerate their treatment.
5. Had to be able to self-administer or has caregiver who can reliably administer subcutaneous injections.
6. Had to be able and willing to give written informed consent and to comply with the requirements of this study protocol.
7. Female had to be either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug. Examples of approved methods of birth control included the following:

   * Condoms, sponge, foams, jellies, diaphragm or intrauterine device
   * Oral, parenteral or intravaginal contraceptives for 90 days prior to study drug administration
   * A vasectomized partner
8. The results of the serum pregnancy test performed at the Screening Visit and urine pregnancy test performed at the Baseline Visit had to be negative.
9. Judged to be in generally good health as determined by the principal investigator

Exclusion Criteria:

1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or is planning bowel surgery.
2. Received infliximab or any other anti-TNF agent or any biological therapy in the past.
3. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.
4. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline.
5. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
6. Received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the Screening endoscopy and during the remainder of the Screening Period.
7. Current diagnosis of fulminant colitis and/or toxic megacolon.
8. Participants with disease limited to the rectum (ulcerative proctitis).
9. Current diagnosis of indeterminate colitis.
10. Current diagnosis and/or history of Crohn's disease.
11. Currently receiving total parenteral nutrition.
12. Discontinued use of azathioprine or 6-MP within 28 days of Baseline.
13. Discontinued use of corticosteroid within 14 days of Baseline.
14. Participants using aminosalicylates for less than 90 days prior to Baseline, not on a stable dose for at least 28 days prior to Baseline, or discontinued use within 28 days of Baseline.
15. Participants with positive Clostridium difficile stool assay.
16. Infections requiring treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to Baseline or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to Baseline.
17. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy/flexible sigmoidoscopy showed evidence of dysplasia or a malignancy, the participant was not to be enrolled in the study.
18. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus, immunodeficiency syndrome, central nervous system demyelinating disease, or untreated tuberculosis (TB).
19. Female participants who was pregnant or breast-feeding or considering becoming pregnant during the study. There should be at least a 150-day period between the last dose of study drug and either conception or initiation of breast-feeding in women of childbearing potential.
20. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable ischemic heart disease, moderate to severe congestive heart failure, recent cerebrovascular accident and any other condition, which in the opinion of the investigator, would put the participant at risk by participation in the protocol.
21. Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever is longer).
22. History of clinically significant drug or alcohol abuse during the previous year.
23. Participants with known hypersensitivity to the excipients of adalimumab as stated in the label.
24. Participants with any prior exposure to Tysabri® (natalizumab).
25. Participants currently taking both budesonide and prednisone (or equivalent) simultaneously.

Answer: D