A Study to Assess Whether Etrolizumab is a Safe and Efficacious Treatment for Participants With Moderately to Severely Active Crohn's Disease
(BERGAMOT Trial)

Recruiting in Palo Alto (17 mi)

+410 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Hoffmann-La Roche

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

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

Treatment Details

Interventions

Etrolizumab (Monoclonal Antibodies)

Participant Groups

11Treatment groups

Experimental Treatment

Placebo Group

Group I: Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mgExperimental Treatment1 Intervention

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.

Group II: Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mgExperimental Treatment2 Interventions

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.

Group III: Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mgExperimental Treatment2 Interventions

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.

Group IV: Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mgExperimental Treatment2 Interventions

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.

Group V: Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mgExperimental Treatment2 Interventions

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.

Group VI: Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mgExperimental Treatment2 Interventions

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.

Group VII: Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mgExperimental Treatment2 Interventions

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.

Group VIII: Induction Phase - Cohort 3 (Pivotal): PlaceboPlacebo Group1 Intervention

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.

Group IX: Maintenance Phase - Placebo Responders: PlaceboPlacebo Group1 Intervention

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.

Group X: Induction Phase - Cohort 1 (Exploratory): PlaceboPlacebo Group1 Intervention

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.

Group XI: Maintenance Phase - Etrolizumab Responders: PlaceboPlacebo Group1 Intervention