An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to
treat people who have ulcerative colitis. This study will look at the stool frequency, rectal
bleeding and findings on endoscopy of people who take vedolizumab compared to those who take
adalimumab.

The study will enroll approximately 658 participants. Participants will be randomly assigned
(by chance, like flipping a coin) to one of the two treatment groups—which will remain
undisclosed to the patient and study doctor during the study (unless there is an urgent
medical need):

- Vedolizumab 300 mg IV

- Adalimumab 160 mg on Day 1 followed by 80 mg on Week 2 then 40 mg every 2 weeks SC

All participants will receive 1 intravenous infusion on Day 1 and Weeks 2, 6, 14, 22, 30, 38,
and 46. All participants will also receive 4 SC injections on Day 1 or 2 SC injections each
on Days 1 and 2, followed by 2 SC injections in 1 day on Week 2 and then 1 SC injection every
2 weeks for up to Week 50. All participants will be asked to record the symptoms of
ulcerative colitis in a daily diary.

This multi-center trial will be conducted worldwide. The overall time to participate in this
study is 79 weeks. Participants will make approximately 11 visits to the clinic, and will be
contacted by telephone 6 months after last dose of study drug for a follow-up assessment.

Inclusion Criteria:

1. Has a diagnosis of ulcerative colitis established at least 3 months prior to screening
by clinical and endoscopic evidence and corroborated by a histopathology report.

2. Has moderately to severely active ulcerative colitis as determined by a Mayo score of
6 to 12 with an endoscopic subscore greater than or equal to >=2 within 14 days prior
to the randomization.

3. Has evidence of ulcerative colitis proximal to the rectum (>=15 centimeter [cm] of
involved colon).

4. With extensive colitis (up to the hepatic flexure) or pancolitis of >8 years duration
or left-sided colitis of >12 years duration must have documented evidence that a
surveillance colonoscopy was performed within 12 months of the initial screening visit
(may be performed during the Screening Period).

5. The participant:

1. Has had previous treatment with tumor necrosis factor- alpha (TNF-alpha)
antagonists without documented clinical response to treatment (example, due to
lack of response [primary nonresponders], loss of response, or intolerance
[secondary nonresponders]), or

2. Has previously used a TNF-alpha antagonists (except adalimumab), and discontinued
its use due to reasons other than safety, or

3. Is naïve to TNF-alpha antagonist therapy but is failing current treatment
(example, corticosteroids, 5-aminosalicylate [5-ASA], or immunomodulators).

Exclusion Criteria:

1. Clinical evidence of abdominal abscess or toxic megacolon at Screening.

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 microscopic
colitis.

5. Has received any of the following for the treatment of underlying disease within 30
days of randomization:

1. Non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide) other
than those specifically listed in Section Permitted Medications For Treatment of
UC.

2. An approved non-biologic therapy in an investigational protocol.

6. Has received any investigational or approved biologic or biosimilar agent within 60
days or 5 half lives prior to the screening (whichever is longer).

7. Has previously received natalizumab, efalizumab, adalimumab, AMG-181, anti-mucosal
addressin cell adhesion molecule-1 antibodies, or rituximab.

8. Has previously received vedolizumab.

9. Has history or evidence of adenomatous colonic polyps that have not been removed, or
colonic mucosal dysplasia.

10. Evidence of an active infection during Screening.

11. Evidence of, or treatment for, Clostridium difficile (C. difficile) or other
intestinal pathogen within 28 days prior to the 1st dose of study drug.

12. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV)
infection (* HBV immune participants, ie, being hepatitis B surface antigen [HBsAg],
may participate).

13. Has active or latent TB, regardless of treatment history.

14. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid
enemas/suppositories within 2 weeks of the administration of the 1st dose of study
drug.

15. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom
checklist prior to the administration of the first dose of study drug.