Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Double-Blind, Placebo-Controlled, Ascending-Dose, Repeat-Dose Safety and Pharmacokinetic Investigation of a Delayed-Release, Enteric-Coated Capsule Formulation of AVX 470 [Anti-TNF (Tumor Necrosis Factor) Globulin (Bovine)] in Patients With Active Ulcerative Colitis
Brief Summary: The purpose of this study is to evaluate the safety and tolerability as well as the pharmacodynamic effects of multiple doses of AVX-470 administered orally in patients with active ulcerative colitis.


Options:
A: 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 (5-ASAs), oral corticosteroids, 6-mercaptopurine (6-MP) and azathioprine (AZA)
* 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 TB

Exclusion Criteria:

* Participants with previous 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 (cm) 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
B: Inclusion Criteria:

* Men or women aged 18 75, inclusive
* Established diagnosis of ulcerative colitis involving the sigmoid colon or proximal segments of bowel
* Total Mayo score between 5-12, inclusive, with endoscopic subscore of the Mayo score ≥ 2 and \> 15 cm of involvement beyond the anal verge

Exclusion Criteria:

* Women with a positive pregnancy test, who are breastfeeding, or who intend to become pregnant during the course of the study
* Diagnosis of Crohn's disease, microscopic colitis or indeterminate colitis
* Presence of ileostomy or colostomy, or history of prior colon resection
* Patients with planned hospitalization or surgery during the course of the study
* Known allergy to milk proteins, red meat or cornstarch
* Stools positive for enteric infection, including parasitic, or C. difficile toxin within 28 days of screening
* Documented presence of Hetatitis B (HBsAg), Hepatitis C (HCV), or HIV
* Presence of dysplasia of any grade on colonoscopic biopsies
* Treatment for cancer (excluding non-melanomatous cancer of the skin or cervical carcinoma in situ) or lymphoproliferative disorder (including lymphoma) within 5 years
* History of tuberculosis (TB) or Listeria infection, or known exposure to another person with active TB disease within 12 weeks of screening; or history of past or current infection with different opportunistic infections
* History of TNF inhibitor (infliximab, adalimumab or certolizumab pegol) use with primary treatment failure. Secondary treatment failures due to intolerance, allergic reaction, or loss of response will not constitute a basis for exclusion. Oral immunosuppressives, mesalamine, and corticosteroids (up to 20mg of prednisone per day) will be permitted so long as these medications are stable for defined periods of time before study participation commences.
C: Inclusion Criteria:

* Diagnosis of moderate to severe ulcerative colitis outpatient
* Disease duration at time of screening of \>/= 12 weeks

Exclusion Criteria:

* Extensive colonic resection or subtotal or total colectomy
* Presence of an ileostomy or colostomy
* Moderate to severe anemia
* A history or evidence of colonic mucosal dysplasia
* Pregnant or lactating
* Significant uncontrolled co-morbidity, such as neurological, cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disorders
* Significant screening ECG abnormalities, including evidence of acute myocardial infarction, complete left bundle branch block, second-degree heart block, or complete heart block
* Poorly controlled diabetes
* Impaired renal function
* Impaired hepatic function in the absence of a diagnosis of primary sclerosing cholangitis
* Positive tests for antibodies indicating active or prior infection with HIV or hepatitis B (HBV) or C (HCV)
* Positive screening test for latent mycobacterium tuberculosis (TB) infection
* Demyelinating disease
* Received any investigational treatment within 12 weeks prior to initiation of study treatment
* Previous exposure to rhuMAb Beta7
D: 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)

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Answer: B