Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis

Inclusion Criteria:

1. Has a diagnosis of UC established at least 1 month prior to Screening by clinical andendoscopic evidence and corroborated by a histopathology report.
2. Has moderately to severely active UC as determined by a complete Mayo score of 6 to 12with an endoscopic subscore ≥2 within 28 days prior to enrollment.
3. Has evidence of UC proximal to the rectum (≥15 cm of involved colon) prior to start ofvedolizumab IV dosing.
4. Has been determined to be suitable for vedolizumab IV for routine management of UC bytheir physician.
5. Has a family history of colorectal cancer, personal history of increased colorectalcancer risk, age >50 years, or other known risk factor must be up-to-date oncolorectal cancer surveillance (may be performed during screening).
6. Has demonstrated an inadequate response with, lost response to, or intolerance of atleast 1 of the following agents: immunomodulators, corticosteroids, or tumor necrosisfactor-alpha (TNF-α) antagonists. Subject who are naive to TNF-α antagonist therapy orwho have previously failed TNF-α antagonist therapy (including primary and secondarynon-responders or intolerant) may be included. Week 6 Randomized Treatment Period Inclusion Criteria
7. Following Lead-in Period, the subject is assessed as having high vedolizumab drugclearance based on a predefined Week 5 serum vedolizumab concentration threshold (<50microg/mL).
8. Following Lead-in Period, the subject is a non-responder based on partial Mayo scoreat Week 6.

Exclusion Criteria:

1. Has clinical evidence of abdominal abscess or toxic megacolon at the Screening Visit.
2. Has had an extensive colonic resection, subtotal or total colectomy.
3. Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
4. Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis,radiation colitis, diverticular disease associated with colitis, or microscopiccolitis.
5. Has received any of the following for the treatment of underlying disease within 30days of screening:
6. Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide)
7. An approved non-biologic therapy in an investigational protocol.
8. Has received any investigational or approved biologic or biosimilar agent within 60days or 5 half-lives prior to screening (whichever is longer).
9. Has previously had prior exposure to approved or investigational anti-integrinantibodies (e.g. natalizumab, efalizumab, etrolizumab, AMG-181, anti-MAdCAM-1antibodies or rituximab).
10. Has previously received approved or investigational vedolizumab.
11. The subject currently requires or is anticipated to require surgical intervention forUC during the study.
12. Has history or evidence of adenomatous colonic polyps that have not been removed, orcolonic mucosal dysplasia.
13. Has any evidence of an active infection during Screening (eg, sepsis, cytomegalovirus,or listeriosis).
14. Has a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 daysprior to screening, or ongoing chronic infection.
15. Has evidence of active C. difficile as evidenced by positive C. difficile toxin or ishaving treatment for C. difficile infection or other intestinal pathogens duringScreening.
16. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or chronic HBV (HBV immune subjects (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included), orhepatitis C virus (HCV) infection. Subjects with documented successful treatment ofHCV with sustained virological response (SVR) at 26 weeks can be enrolled.
17. Has active or latent tuberculosis (TB), as evidenced by the following: a. A diagnostic TB test performed within 30 days of screening or during the ScreeningPeriod that is positive, defined as: i. Positive QuantiFERON test or 2 successiveindeterminate QuantiFERON tests, OR ii. A TB skin test reaction ≥ 5 mm OR, b. ChestX-ray within 3 months of screening that is suspicious for pulmonary TB, and a positiveor 2 successive indeterminate QuantiFERON tests within 30 days prior to Screening orduring the Screening Period.
18. Has any identified congenital or acquired immunodeficiency (eg, common variableimmunodeficiency, HIV infection, organ transplantation).
19. Has any live vaccination within 30 days prior to Screening or is planning to receiveany live vaccination during participation in the study.
20. Has used a topical (rectal) treatment with (5-ASA) or corticosteroidenemas/suppositories within 2 weeks prior to Screening.
21. Has a history of hypersensitivity or allergies to vedolizumab IV or its components.
22. Has received total parenteral nutrition (TPN) or albumin in the last 30 days prior toscreening.
23. Has any unstable or uncontrolled cardiovascular disorder, heart failure moderate tosevere (New York Class Association III or IV), any pulmonary, hepatic, renal, GI,genitourinary, hematological, coagulation, immunological, endocrine/metabolic, orother medical disorder that, in the opinion of the investigator, would confound thestudy results or compromise subject safety.
24. Has had a surgical procedure requiring general anesthesia within 30 days prior toscreening or is planning to undergo major surgery during the study period.
25. Has a history of malignancy, except for the following: adequately-treatednon-metastatic basal cell skin cancer; squamous cell skin cancer that has beenadequately treated and that has not recurred for at least 1 year prior to Screening;and history of cervical carcinoma in situ that has been adequately treated and thathas not recurred for at least 3 years prior to screening. Subjects with remote historyof malignancy (eg, >10 years since completion of curative therapy without recurrence)will be considered based on the nature of the malignancy and the therapy received andmust be discussed with the sponsor on a case by-case basis prior to Screening.
26. Has a history of any major neurological disorders, including stroke, multiplesclerosis, brain tumor, demyelinating, or neurodegenerative disease.
27. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptomchecklist during Screening or prior to the administration of the first dose of studydrug on Day 1.
28. Has a history of drug abuse (defined as any illicit drug use) or a history of alcoholabuse within 1 year prior to the Screening Visit.