A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors

Inclusion Criteria:

* Diagnosis of ulcerative colitis (UC) established at least 3 months prior to randomization (Day 1)
* Moderately to severely active UC as determined by the MCS
* Naive to treatment with TNF inhibitor therapy
* An inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
* Background UC therapy may include oral 5-aminosalisylate (5-ASA), budesonide, oral corticosteroids, probiotics, azathioprine (AZA), 6-mercaptopurine (6MP), or methotrexate (MTX) if doses have been stable for:
* AZA, 6-MP, MTX: 8 weeks immediately prior to randomization
* 5-ASA: 4 weeks immediately prior to randomization
* Corticosteroids: 4 weeks immediately prior to randomization; if corticosteroids are being tapered, dose has to be stable for at least 2 weeks prior to randomization
* Use of highly effective contraception method as defined by the protocol
* Have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening

Exclusion Criteria:

Exclusion Criteria Related to Inflammatory Bowel Disease:

* Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for UC
* Past or present ileostomy or colostomy
* Diagnosis of indeterminate colitis
* Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
* Diagnosis of toxic megacolon within 12 months of initial screening visit
* Any diagnosis of Crohn's disease
* Past or present fistula or abdominal abscess
* A history or current evidence of colonic mucosal dysplasia
* Patients with any stricture (stenosis) of the colon
* Patients with history or evidence of adenomatous colonic polyps that have not been removed

Exclusion Criteria Related to Prior or Concomitant Therapy:

* Prior treatment with TNF-alpha antagonists
* Any prior treatment with etrolizumab or other anti-integrin agents
* Any prior treatment with rituximab
* Any treatment with tofacitinib during screening
* Any prior treatment with anti-adhesion molecules
* Use of intravenous (IV) steroids within 30 days prior to screening with the exception of a single administration of IV steroid
* Use of agents that deplete B or T cells
* Use of anakinra, abatacept, cyclosporine, sirolimus, or mycophenolate mofetil (MMF) within 4 weeks prior to randomization
* Chronic nonsteroidal anti-inflammatory drug (NSAID) use
* Patients who are currently using anticoagulants including, but not limited to, warfarin, heparin, enoxaparin, dabigatran, apixaban, rivaroxaban
* Patients who have received treatment with corticosteroid enemas/suppositories and/or topical (rectal) 5-ASA preparations within 2 weeks prior to randomization
* Apheresis (i.e., Adacolumn apheresis) within 2 weeks prior to randomization
* Received any investigational treatment including investigational vaccines within 5 half lives of the investigational product or 28 days after the last dose, whichever is greater, prior to randomization
* History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or hypersensitivity to etrolizumab (active drug substance) or any of the excipients (L histidine, L-arginine, succinic acid, polysorbate 20)
* Patients administered tube feeding, defined formula diets, or parenteral alimentation/nutrition who have not discontinued these treatments within 3 weeks prior to randomization

Exclusion Criteria Related to General Safety:

* Pregnant or lactating
* Lack of peripheral venous access
* Hospitalization (other than for elective reasons) during the screening period
* Significant uncontrolled comorbidity, such as cardiac (e.g., moderate to severe heart failure New York Heart Association Class III/IV), pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders
* Neurological conditions or diseases that may interfere with monitoring for PML
* History of demyelinating disease
* Clinically significant abnormalities on screening neurologic examination (PML Objective Checklist)
* Clinically significant abnormalities on the screening PML Subjective Checklist
* History of alcohol, drug, or chemical abuse less than 6 months prior to screening
* Conditions other than UC that could require treatment with \>10 mg/day of prednisone (or equivalent) during the course of the study
* History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening

Exclusion Criteria Related to Infection Risk

* Congenital or acquired immune deficiency
* Patients must undergo screening for HIV and test positive for preliminary and confirmatory tests
* Positive hepatitis C virus (HCV) antibody test result
* Positive hepatitis B virus (HBV) antibody test result
* Evidence of or treatment for Clostridium difficile (as assessed by C. difficile toxin testing) within 60 days prior to randomization or other intestinal pathogens (as assessed by stool culture and ova and parasite evaluation) within 30 days prior to randomization
* Evidence of or treatment for clinically significant cytomegalovirus (CMV) colitis (based on the investigator's judgment) within 60 days prior to randomization
* History of active or latent TB
* History of recurrent opportunistic infections and/or history of severe disseminated viral infections
* Any serious opportunistic infection within the last 6 months prior to screening
* Any current or recent signs or symptoms (within 4 weeks before screening and during screening) of infection
* Any major episode of infection requiring treatment with IV antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
* Received a live attenuated vaccine within 4 weeks prior to randomization
* History of organ transplant

Exclusion Criteria Related to Laboratory Abnormalities (at Screening)

* Serum creatinine \>2 x upper limit of normal (ULN)
* ALT or AST \>3 x ULN or alkaline phosphatase \>3 x ULN or total bilirubin \>2.5 x ULN
* Platelet count \<100,000/uL
* Hemoglobin \<8 g/dL
* Absolute neutrophil count \<1500/uL
* Absolute lymphocyte count \<500/uL