A Study to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis

Inclusion Criteria:

- Confirmed diagnosis of UC at least 12 weeks before screening based on clinical,
endoscopic, and histopathological evidence.

- Have a 3-component Mayo score of 4 to 9, which includes a modified Mayo Endoscopy
Score (mMES) of ≥ 2 as determined by a central reader, a rectal bleeding score of ≥ 1,
and a stool frequency score of ≥ 1.

- Must have failed or be intolerant to (discontinued the medication due to an adverse
event as determined by the investigator) at least 1 of the following treatments for UC
within 5 years of the screening visit: Oral corticosteroids, azathioprine or
6-mercaptopurine, biologic therapy (eg, infliximab, vedolizumab or adalimumab).

- Participants currently receiving the following treatment(s) for UC are eligible,
provided they have been receiving acceptable and stable dose(s): oral 5-ASA or oral
corticosteroids.

- No evidence of active or latent or inadequately treated tuberculosis infection.

- Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

- Clinical signs of fulminant colitis or toxic megacolon.

- Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious
colitis, or clinical or radiographic findings suggestive of Crohn's disease.

- Disease limited to the distal 15 cm of the colon.

- Receiving (or expected to receive) the following therapies within protocol-designated
timeframes before the baseline visit or during the study: anti-adhesion molecule
therapy; anti-TNF therapy; interferon therapy; cyclosporine, mycophenolate, or
tacrolimus; daily dose of oral corticosteroids ≥ 30 mg prednisone or equivalent;
intravenous corticosteroids; rectally administered formulation of corticosteroids or
5-aminosalicylic acid; and AZA, 6-MP, or methotrexate.

- Enema treatments within 2 weeks of the baseline visit, with the exception of enema
bowel preparations for clinical assessments.

- Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or
Clostridium difficile toxin at the screening visit.

- Other immunocompromised states and history of opportunistic infections.

- History of stomach or intestinal surgery, including bariatric surgery (Note:
appendectomy and/or cholecystectomy, is allowed).

- If at risk for colorectal cancer, must have had a colonoscopy within protocol-defined
timeframes.

- History of recurrent, disseminated, or multiple dermatomal herpes zoster.

- History of alcohol or drug abuse.

- History of active malignancy within 5 years of screening, excluding superficial basal
and squamous cell carcinoma of the skin and adequately treated carcinoma in situ of
the cervix.

- Current or recent history (within 30 days before randomization) of a clinically
meaningful viral, bacterial, fungal, parasitic, or mycobacterial infection.

- Previously received either lymphocyte apheresis or selective monocyte granulocyte
apheresis (eg, Cellsorba) within 1 year of baseline.

- History of unstable ischemic heart disease or uncontrolled hypertension.

- Positive serology test results for HIV, for hepatitis B surface antigen or core
antibody, or for HCV antibody with detectable RNA at screening.

- Participants taking potent systemic CYP3A4 inhibitors or inducers or fluconazole
within 2 weeks or 5 half-lives (whichever is longer) of baseline.

- Participants taking P-gp substrates with narrow therapeutic index, including digoxin
within 2 weeks or 5 half-lives (whichever is longer) of baseline.