Inclusion Criteria:

• Males and females, 18 years of age or older.
• Diagnosis of ulcerative colitis (UC) verified by endoscopy within 60 months prior to consent.
• Severe active disease, as defined by a Modified Truelove & Witts Severity Index (MTWSI; also known as Lichtiger score) ≥ 11 at consent, with a confirmatory MTWSI ≥ 10 on or after the fifth consecutive day of intravenous (IV)steroids and within 1 day prior to randomization.
• Mayo score ≥ 10 and Mayo mucosal subscore ≥ 2 after a minimum of 3 consecutive days (ie, on or after the fourth consecutive day) of IV steroids.
• Adequate contraception from the day of consent through 3 months after the last dose of study drug.
• Negative serum pregnancy test.
• Negative Clostridium difficile test.
• Signed and dated informed consent and Health Insurance Portability and Accountability Act (HIPAA) if applicable.

Exclusion Criteria:

• UC requiring immediate intervention or toxic megacolon requiring imminent intervention.
• History of total proctocolectomy, or subtotal colectomy with ileorectal anastomosis.
• Presence of Ileostomy.
• White blood cell count less than 2.5 x 10^3/mcL; platelet count less than 150 x 10^3/mcL; or hemoglobin level less than 8 g/dL.
• Active medically significant infections, particularly those of viral etiology, eg, known cytomegalovirus (CMV) colitis. This includes any incidence of medically significant opportunistic infections within the past 12 months.
• Live vaccination within 6 weeks prior to randomization.
• Significant organ dysfunction, including cardiac, renal, liver, central nervous system (CNS), pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality.
• History of myocardial infarction, coronary artery disease, congestive heart failure, or arrythmias within 6 months prior to consent.
• History or treatment of lymphoproliferative disorder (LPD) or malignancy within the past 5 years (excluding nonmelanoma skin cancer or carcinoma in situ of the cervix).
• Seropositivity for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV).
• Pregnancy or nursing.
• Treatment with a first dose of infliximab or another anti-tumor necrosis factor (TNF)-α drug within 4 weeks of randomization, or treatment with a subsequent dose of an anti-TNF-α drug within 2 weeks of randomization.
• Treatment with cyclosporine or tacrolimus (FK506) within 2 weeks prior to randomization.
• Treatment with any other investigational drugs or therapies within 60 days prior to randomization, except those mentioned in the two exclusion criteria above.
• Unable or willing to discontinue any UC drug (including, but not limited to 6-mercaptopurine, azathioprine, or methotrexate), except glucocorticoids or 5-ASA, immediately prior to randomization.
• Nontherapeutic levels of chronic antiseizure medications in subjects with a prior history of seizures.
• Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation.