A Study to Assess Whether Etrolizumab is a Safe and Efficacious Treatment for Participants With Moderately to Severely Active Crohn's Disease
Condition: Crohn Disease
MeSH terms: Crohn Disease
Intervention: Etrolizumab; Placebo
Intervention description: Etrolizumab will be administered as per regimen specified in individual arms.; Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Intervention MeSH terms: Etrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1035.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This is a multicenter, Phase 3, double-blind, placebo-controlled study evaluating the
      efficacy, safety, and tolerability of etrolizumab compared with placebo during induction and
      maintenance treatment of moderately to severely active Crohn's Disease (CD). The target
      population includes participants with CD who are refractory or intolerant to corticosteroids
      (CS) and/or immunosuppressant (IS) therapy and who have either not received prior anti-tumor
      necrosis factor (anti-TNF) therapy (TNF-naive) or who have had prior exposure to anti-TNF
      therapies and demonstrated inadequate responses or intolerance to anti-TNFs.

      The study period will consist of a Screening Phase (up to 35 days) plus (+) a 14-week
      Induction Phase + a 52-week Maintenance Phase + a 12-week Safety Follow-up Phase. At Week 14
      (end of Induction Phase), participants achieving a decrease from baseline of at least 70
      points in the Crohn's Disease Activity Index (CDAI) score (CDAI-70 response) without the use
      of rescue therapy will continue to the Maintenance Phase.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Moderately to severely active Crohn's Disease (CD) as determined by the CDAI, patient
             reported outcomes and endoscopically defined disease activity in the ileum and/or
             colon

          -  Intolerance, refractory disease, or no response to corticosteroids (CS),
             immunosuppressants (IS), or anti-TNF therapy within 5 years from screening.
             Participants who have not previously demonstrated inadequate response or intolerance
             to one or more anti-TNF therapies are eligible to participate in the study provided
             they are intolerant or refractory to CS or IS therapy

          -  Use of effective contraception as defined by the protocol

        Exclusion Criteria:

          -  A history of, or current conditions affecting the digestive tract, such as ulcerative
             colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess,
             adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel
             syndrome

          -  Planned surgery for CD

          -  Ileostomy or colostomy

          -  Has received non-permitted inflammatory bowel disease (IBD) therapies (including
             natalizumab, vedolizumab, and efalizumab, as stated in the protocol)

          -  Any prior treatment with ustekinumab within 14 weeks prior to randomization

          -  Chronic hepatitis B or C infection, human immunodeficiency virus (HIV), active or
             latent tuberculosis (participants with prior history of Bacillus Calmette-Guérin [BCG]
             vaccination must pass protocol-defined screening criteria)

          -  Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical
             judgment of the investigator. Fistulas related to CD are not exclusionary

          -  Any prior treatment with anti-adhesion molecules (e.g., anti-mucosal addressin cell
             adhesion molecule [anti-MAdCAM-1])

          -  Any major episode of infection requiring treatment with intravenous antibiotics ≤8
             weeks prior to screening or oral antibiotics ≤4 weeks prior to screening. Treatment
             with antibiotics as adjunctive therapy for CD in the absence of documented infection
             is not exclusionary

          -  Hospitalization (other than for elective reasons) within 4 weeks prior to
             randomization