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: 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: Natalizumab; anti-TNF therapy; Vedolizumab or any investigational anti-adhesion molecule therapy; Ustekinumab or any on or off label biologic therapy; interferon therapy; cyclosporine, mycophenolate, or tacrolimus; daily dose of oral corticosteroids ≥ 25 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). o surgery for UC or likely to require surgery for UC during the study. * 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.