Efficacy and Safety of Vedolizumab Subcutaneously (SC) as Maintenance Therapy in Ulcerative Colitis

The drug being tested in this study is called vedolizumab subcutaneous (vedolizumab SC).
Vedolizumab SC is being tested to treat people who have moderate to severely active
ulcerative colitis. This study will look at clinical remission as well as mucosal healing,
durable clinical response, durable clinical remission, and corticosteroid free remission in
participants with UC who receive vedolizumab SC maintenance therapy after having achieved a
clinical response to vedolizumab IV induction therapy.

The study will enroll approximately 400 patients. All participants will enter into a 6 week
Induction Phase where they will be administered open-label vedolizumab IV 300 mg via
intravenous infusion (IV) at Week 0 (Day 1) and Week 2 (day 15), and will then be assessed
for a clinical response at Week 6. Participants who achieve a clinical response at Week 6
will be randomly assigned to one of the three treatment groups:

- Vedolizumab SC 108 mg Q2W and Placebo IV Q8W

- Vedolizumab IV 300 mg Q8W and Placebo SC Q2W

- Placebo SC Q2W and Placebo IV Q8W

Participants who do not achieve a clinical response at Week 6 will not be randomized in to
the Maintenance Period, and will receive a third infusion of vedolizumab IV 300 mg at Week 6.

This multi-center trial will be conducted worldwide. The overall time to participate in this
study is up to 71 weeks. Participants will make multiple visits to the clinic, plus a final
visit 18 weeks after last dose of study drug for a follow-up assessment. Participants will
also participate in a long-term safety follow-up, by phone, at 6 months after the last dose
of study drug.

Inclusion Criteria:

1. Diagnosis of ulcerative colitis (UC) established at least 6 months prior to screening,
by clinical and endoscopic evidence and corroborated by a histopathology report.

2. Moderately to severely active UC as determined by a complete Mayo score of 6-12 (with
an endoscopic subscore ≥2)

3. Evidence of UC extending proximal to the rectum (≥15 cm of involved colon).

4. Inadequate response with, loss of response to, or intolerance to corticosteroids,
immunomodulators, or Tumor Necrosis Factor-alpha (TNF-α) antagonists

Exclusion Criteria:

1. Evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.

2. Extensive colonic resection, subtotal or total colectomy.

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

4. Prior exposure to investigational or approved non-biologic therapies (eg,
cyclosporine, tacrolimus, thalidomide, methotrexate or tofacitinib) for the treatment
of underlying disease within 30 days or 5 half-lives of screening (whichever is
longer).

5. Prior exposure to any investigational or approved biologic or biosimilar agent within
60 days or 5 half-lives of screening (whichever is longer).

6. Prior exposure to vedolizumab

7. Surgical intervention for UC required at any time during the study.

8. History or evidence of adenomatous colonic polyps that have not been removed, or has a
history or evidence of colonic mucosal dysplasia.

9. Suspected or confirmed diagnosis of Crohn's entercolitis, indeterminate colitis,
ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or
microscopic colitis.

10. Active infections

11. Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV)
infection, HIV or tuberculosis (active or latent), identified congenital or acquired
immunodeficiency. HBV immune participants (ie, being hepatitis B surface antigen
[HBsAg] negative and hepatitis B antibody positive) may, however, be included.

12. History of any major neurological disorders, including stroke, multiple sclerosis,
brain tumor, demyelinating or neurodegenerative disease.