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 toat least 1, but no more than 2 TNFα antagonists. Participants without prior failureor intolerance to biologics are not eligible. Participants who discontinued TNFαantagonist therapy for reasons other than failure or intolerance (eg, pregnancy) maybe eligible after discussion with the medical monitor. Note: After the interim analysis, participants with inadequate response, loss ofresponse, or intolerance to conventional UC therapy without prior exposure tobiologics may be enrolled if deemed appropriate. Participants who discontinuedbiologics for reasons other than failure or intolerance (eg, pregnancy) may beeligible after discussion with the Medical Monitor.

7. If using corticosteroids must be on a stable dose of oral corticosteroids up to amaximum of 40 mg daily of prednisone or 9 mg daily of budesonide, or equivalent forat least 2 weeks prior to screening endoscopy and must be willing to follow amandatory taper of 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 an 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. Participants with a history ofcolonic mucosal dysplasia are also excluded.

8. Has uncontrolled primary sclerosing cholangitis.

Infectious Disease Exclusion Criteria:

1. Has any evidence of an active systemic infection during screening. Participants withnonsystemic infections (eg, active fungal infection of nail beds) may be eligible,if in the opinion of the investigator, inclusion of the participant will notinterfere with the collection or interpretation of study results and poses no riskto the participant.

2. Has active or latent tuberculosis (TB), regardless of treatment history, asevidenced by any of the following:

3. History of TB.

4. A diagnostic TB test performed during screening that is positive, as definedby: i. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests orii. A tuberculin skin test reaction ≥10 mm (≥5 mm in subjects receiving theequivalent of >15 mg daily prednisone).

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

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

7. Evidence of, or treatment for, Clostridium difficile infection or other intestinalpathogen within 28 days prior to first dose of study treatment. Participants whotest positive for C. difficile or other intestinal pathogens at screening andreceive treatment may be enrolled or rescreened (if required) following confirmationof infection resolution.

8. 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, except for any CYP3A4 modulator used to treat a C. difficile or anintestinal pathogen infection at screening.

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. Chronic NSAID use defined as daily use for >2 consecutive weeks (Note:occasional use [<2 consecutive weeks] of NSAIDs and acetaminophen [<100 mgdaily] for headache, arthritis, myalgias, or menstrual cramps and chronic lowdose aspirin use [81-162.5 mg daily] for cardiovascular prophylaxis arepermitted).

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 last dose.

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 that, in theinvestigator's opinion, may interfere with interpretation of study results.