Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg
Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one subcutaneous (SC) injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Experimental
Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg
Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Placebo Comparator
Induction Phase - Cohort 1 (Exploratory): Placebo
Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Experimental
Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg
Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking for the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Experimental
Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg
Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Experimental
Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg
Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Experimental
Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg
Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Placebo Comparator
Induction Phase - Cohort 3 (Pivotal): Placebo
Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Placebo Comparator
Maintenance Phase - Placebo Responders: Placebo
Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 will undergo a sham randomization into the Maintenance Phase. Placebo responders from induction will receive blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64.
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Placebo Comparator
Maintenance Phase - Etrolizumab Responders: Placebo
Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64.
  • Drug: Placebo
    Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Experimental
Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg
Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other names:
    • RO5490261
    • RG7413

More Details

Status
Completed
Sponsor
Hoffmann-La Roche

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.