A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Etrozulimab; Placebo
Intervention description: Participants will receive 105 mg etrolizumab administered by SC injection Q4W.; Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
Intervention MeSH terms: Etrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 609.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This Phase III, double-blind, placebo-controlled, multicenter study will investigate the
      efficacy and safety of etrolizumab during induction and maintenance of remission compared
      with placebo in the treatment of participants with moderately to severely active ulcerative
      colitis (UC) who have been previously exposed to TNF inhibitors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of UC established at least 3 months prior to Day 1

          -  Moderately to severely active UC as determined by the Mayo Clinic Score (MCS)
             assessment

          -  Treatment within 5 years prior to screening with one or two induction regimens that
             contain TNF inhibitors (including TNF inhibitor biosimilars)

          -  Washout of anti-TNF therapy for at least 8 weeks preceding Day 1

          -  Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral
             corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP),
             or methotrexate (MTX) if doses have been stable during the screening period

          -  Use of highly effective contraception as defined by the protocol

          -  Must 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:

          -  A history of or current conditions and diseases affecting the digestive tract, such as
             indeterminate colitis, suspicion of ischemic colitis, radiation colitis, or
             microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal
             dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic
             polyps

          -  Prior or planned surgery for UC

          -  Past or present ileostomy or colostomy

          -  Any prior treatment with etrolizumab or other anti-integrin agents (including
             natalizumab, vedolizumab, and efalizumab)

          -  Any prior treatment with anti-adhesion molecules (e.g. anti-MAdCAM-1)

          -  Any prior treatment with rituximab

          -  Any treatment with tofacitinib during screening

          -  Congenital or acquired immune deficiency, chronic hepatitis B or C infection, human
             immunodeficiency virus (HIV) positive, or history of tuberculosis (active or latent)

          -  Evidence of or treatment for Clostridium difficile or clinically significant
             cytomegalovirus (CMV) colitis within 60 days prior to Day 1

          -  Evidence of or treatment for other intestinal pathogens within 30 days prior to Day 1

          -  History of recurrent opportunistic infections and/or severe disseminated viral
             infections

          -  History of organ transplant

          -  Any major episode of infection requiring treatment with intravenous (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 Day 1