• Percentage of Participants with Sustained Remission [ Time Frame: At Weeks 8 and 30 ]
• Percentage of Participants with Clinical Response at Weeks 8 and 30 [ Time Frame: At Weeks 8 and 30 ]
• Percentage of Participants with Endoscopic Healing at Weeks 8 and 30 [ Time Frame: At Weeks 8 and 30 ]
• Percentage of Participants with Endoscopic Remission at Weeks 8 and 30 [ Time Frame: At Weeks 8 and 30 ]
• Change From Baseline in UC Bowel Movement Signs and Symptoms at Weeks 8 and 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score [ Time Frame: Baseline to Weeks 8 and 30 ]
  The UC-PRO/SS is a 9-item questionnaire containing two domains: bowel movement signs and symptoms (6 items) and abdominal symptoms (3 items). An average score is calculated for each domain; a higher score indicates worse symptoms.
• Change From Baseline in UC Abdominal Signs and Symptoms at Weeks 8 and 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score [ Time Frame: Baseline to Weeks 8 and 30 ]
  The UC-PRO/SS is a 9-item questionnaire containing two domains: bowel movement signs and symptoms (6 items) and abdominal symptoms (3 items). An average score is calculated for each domain; a higher score indicates worse symptoms.
• Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Weeks 8 and 30 [ Time Frame: Baseline to Weeks 8 and 30 ]
  The IBDQ is a 32-item questionnaire containing four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale; a higher score indicating better health-related quality of life.
• Percentage of Participants with Adverse Events [ Time Frame: Up to 30 weeks ]
• Percentage of Participants with Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration [ Time Frame: At Baseline, Weeks 2, 4, 8, 14, 22, and 30 (up to 30 weeks) ]
• Maximum Serum Concentration (Cmax) of UTTR1147A [ Time Frame: Postdose at Baseline and Week 8 ]
• Minimum Serum Concentration (Cmin) of UTTR1147A [ Time Frame: Predose in Part A: at Weeks 4 and 8; in Part B: Weeks 14 and 22; and at Week 26 (up to 26 weeks) ]

• Drug: UTTR1147A
  UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.
  Other Names:

  • Efmarodocokin alfa
  • RO7021610
  • RG7880
  • IL-22Fc
• Drug: UTTR1147A Placebo
  The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.
• Drug: Vedolizumab
  Vedolizumab will be administered IV, as specified in the prescribing information.
  Other Name: Entyvio
• Drug: Vedolizumab Placebo
  The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.

• Experimental: Arm 1a: UTTR1147A Dose Level 1 (Part A) + UTTR1147A (Part B)

  Part A: UTTR1147A dose level 1 and Vedolizumab Placebo.

  Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.

  Interventions:

  • Drug: UTTR1147A
  • Drug: Vedolizumab Placebo
• Experimental: Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B)

  Part A: UTTR1147A dose level 1 and Vedolizumab Placebo.

  Part B: UTTR1147A Placebo and Vedolizumab Placebo.

  Interventions:

  • Drug: UTTR1147A
  • Drug: UTTR1147A Placebo
  • Drug: Vedolizumab Placebo
• Experimental: Arm 2a: UTTR1147A Dose Level 2 (Part A) + UTTR1147A (Part B)

  Part A: UTTR1147A dose level 2 and Vedolizumab Placebo.

  Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.

  Interventions:

  • Drug: UTTR1147A
  • Drug: Vedolizumab Placebo
• Experimental: Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B)

  Part A: UTTR1147A dose level 2 and Vedolizumab Placebo.

  Part B: UTTR1147A Placebo and Vedolizumab Placebo.

  Interventions:

  • Drug: UTTR1147A
  • Drug: UTTR1147A Placebo
  • Drug: Vedolizumab Placebo
• Experimental: Arm 3a: UTTR1147A Dose Level 3 (Part A) + UTTR1147A (Part B)

  Part A: UTTR1147A dose level 3 and Vedolizumab Placebo.

  Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.

  Interventions:

  • Drug: UTTR1147A
  • Drug: Vedolizumab Placebo
• Experimental: Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B)

  Part A: UTTR1147A dose level 3 and Vedolizumab Placebo.

  Part B: UTTR1147A Placebo and Vedolizumab Placebo.

  Interventions:

  • Drug: UTTR1147A
  • Drug: UTTR1147A Placebo
  • Drug: Vedolizumab Placebo
• Active Comparator: Arm 4: Vedolizumab
  Parts A and B: Vedolizumab and UTTR1147A Placebo.
  Interventions:

  • Drug: UTTR1147A Placebo
  • Drug: Vedolizumab
• Placebo Comparator: Arm 5: Placebo
  Parts A and B: UTTR1147A Placebo and Vedolizumab Placebo.
  Interventions:

  • Drug: UTTR1147A Placebo
  • Drug: Vedolizumab Placebo

Inclusion Criteria:

• Diagnosis of UC
• Confirmation of moderately to severely active UC, defined by the Mayo Clinic Score
• Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, or tumor necrosis factor [TNF] inhibitors [maximum of 2 prior TNF inhibitors]) and/or corticosteroid treatment
• Use of highly effective contraception as defined by the protocol

Exclusion Criteria:

• History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year; or primary sclerosing cholangitis
• History of cancer as defined by the protocol
• Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC)
• Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC
• Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis or toxic megacolon within 12 months prior to screening
• Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
• Current fistula or history of fistula, pericolonic abscess and stricture (stenosis) of the colon
• History or current evidence of unresectable colonic mucosal dysplasia or history of high-grade colonic mucosal dysplasia
• Prior treatment with UTTR1147A
• Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents
• Prior treatment with rituximab
• Use of prohibited therapies, as defined by the protocol, prior to randomization
• Congenital or acquired immune deficiency
• Evidence or treatment of infections or history of infections, as defined by the protocol