A Study of Vedolizumab With Tofacitinib in Adults With Ulcerative Colitis (UC)

Inclusion Criteria:

1. Has a confirmed diagnosis of UC established at least 3 months prior to screening, byclinical and endoscopic evidence and corroborated by a histopathology report.

2. Has moderately to severely active UC as determined by a complete Mayo score [including physician's global assessment (PGA)] of 6 to 12 with a rectal bleedingsubscore ≥>1 and a centrally assessed endoscopic subscore ≥2 at screening.

3. Has evidence of UC extending proximally to the rectum [≥15 centimeter (cm) ofinvolved colon].

4. Participants with extensive colitis or pancolitis of >8 years duration or left sidedcolitis >12 years duration must have documented evidence that a surveillancecolonoscopy was performed within 12 months of the initial screening visit.

5. Participants with a family history of colorectal cancer, personal history ofincreased colorectal cancer risk, age >50 years, or other known risk factors must beup to date on colorectal cancer surveillance.

6. Has demonstrated an inadequate response to, loss of response to, or intolerance tono more than 2 TNF antagonists.

7. If using corticosteroids must be on a stable dose of oral corticosteroids up to amaximum of 20 milligrams per day (mg/day) of prednisone or equivalent for at least 4weeks prior to screening endoscopy and must be willing to follow a mandatory taperof corticosteroids from enrollment.

Exclusion Criteria:

Gastrointestinal Exclusion criteria:

1. Has any of the following UC-related complications:

2. Acute severe UC.

3. The participant has had extensive colonic resection, subtotal or totalcolectomy.

4. The participant has clinical evidence of abdominal abscess or toxic megacolon.

5. The participant has had ileostomy, colostomy, or known fixed symptomaticstenosis of the intestine.

6. Short bowel syndrome.

7. Has Crohn's colitis, indeterminate colitis, ischemic colitis, nonsteroidalanti-inflammatory drug (NSAID) induced colitis, idiopathic colitis (i.e, colitis notconsistent with UC), radiation colitis, microscopic colitis, colonic mucosaldysplasia, or untreated bile acid malabsorption.

8. Has uncontrolled primary sclerosing cholangitis.

Infectious Disease Exclusion Criteria:

1. Has any evidence of an active infection during screening.

2. Has active or latent tuberculosis (TB), regardless of treatment history, asevidenced by any of the following: a. History of TB. b. A diagnostic TB test performed during screening that ispositive, as defined by: i. A positive QuantiFERON test or 2 successiveindeterminate QuantiFERON tests or ii. A tuberculin skin test reaction ≥10 mm (≥5 mmin subjects receiving the equivalent of >15 mg/day prednisone).

3. A positive test for hepatitis B virus (HBV).

4. A positive test for hepatitis C virus (HCV).

5. Evidence of, or treatment for, Clostridium difficile infection or other intestinalpathogen within 28 days prior to first dose of study treatment.

6. Evidence of active Cytomegalovirus (CMV) infection at screening.

Medication exclusion criteria:

1. Has received immunomodulators (eg, 6-mercaptopurine, azathioprine, and methotrexate)within 4 weeks prior to first dose or immunosuppressants (eg, cyclosporine,tacrolimus) within 8 weeks prior to first dose.

2. Any medicinal product, herbal medication, or natural health product which mightinterfere with cytochrome P450 genotype 3A4 (CYP3A4) within 2 weeks prior toenrollment.

3. Has received any of the following medical therapies for UC:

4. IV antibiotics within 8 weeks prior to enrollment.

5. Any rectal therapy for treatment of UC within 2 weeks prior to screeningendoscopy.

6. NSAIDs as long-term treatment, defined as use for at least 4 days a week eachmonth (>100 milligrams (mg) daily or acetaminophen and aspirin >325 mg daily.)

7. Has received a live virus or live bacterial vaccine within 4 weeks prior toenrollment, or planned vaccination during the study and for 12 weeks after lastdose.

General Exclusion Criteria:

1. Has any of the following cardiovascular or thrombotic conditions:

2. Recent (within past 6 months) cerebrovascular accident, myocardial infarction,or coronary stenting.

3. Recent (within past 6 months) moderate to severe congestive heart failure (NewYork Heart Association class III or IV).

4. Prior history of thrombotic events, including deep vein thrombosis andpulmonary embolism.

5. Known inherited conditions that predispose to hypercoagulability.

6. History of lymphoproliferative disease, including lymphoma, or signs and symptomssuggestive of possible lymphoproliferative disease, such as lymphadenopathy and/orsplenomegaly.

7. A surgical procedure requiring general anesthesia within 3 months prior to screeningor is planning to undergo major surgery during the study period.

8. Any investigational procedure ≤4 weeks prior to screening.