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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02394028
Recruitment Status : Recruiting
First Posted : March 20, 2015
Last Update Posted : March 10, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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.


Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Etrolizumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Etrolizumab as an Induction And Maintenance Treatment For Patients With Moderately to Severely Active Crohn's Disease
Actual Study Start Date : March 20, 2015
Estimated Primary Completion Date : June 4, 2021
Estimated Study Completion Date : August 27, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
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

No Intervention: Maintenance Phase - Non-Responders: Safety Follow-Up/GA29145
All participants from Cohorts 1-3 who are considered non-responders after the Induction Phase at Week 14 may be eligible to enter the open-label extension study GA29145 (NCT02403323) and/or undergo a 12-week safety follow-up.



Primary Outcome Measures :
  1. Induction Phase: Percentage of Participants with Clinical Remission at Week 14 [ Time Frame: Baseline and Week 14 ]
    Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

  2. Induction Phase: Percentage of Participants with Endoscopic Improvement at Week 14 [ Time Frame: Baseline and Week 14 ]
    Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.

  3. Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66 [ Time Frame: Baseline and Week 66 ]
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

  4. Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66 [ Time Frame: Baseline and Week 66 ]
    Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score.


Secondary Outcome Measures :
  1. Induction Phase: Percentage of Participants with Clinical Remission at Week 6 [ Time Frame: Baseline and Week 6 ]
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

  2. Induction Phase: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score Greater than (>)1, at Week 14 [ Time Frame: Week 14 ]
  3. Induction Phase: Change from Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 [ Time Frame: Baseline and Week 14 ]
  4. Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66, Among Those who Achieved Clinical Remission at Week 14 [ Time Frame: Baseline, Weeks 14 and 66 ]
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

  5. Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 66, Among Those who Were Receiving Corticosteroids at Baseline [ Time Frame: Baseline and Week 66 ]
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

  6. Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66 Among Participants who Achieved Endoscopic Improvement at Week 14 [ Time Frame: Baseline, Weeks 14 and 66 ]
    Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score.

  7. Maintenance Phase: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score >1, at Week 66 [ Time Frame: Week 66 ]
  8. Maintenance Phase: Percentage of Participants with Durable Clinical Remission [ Time Frame: Week 14 up to Week 66 (assessed at Weeks 24, 28, 32, 44, 56, and 66) ]
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Durable clinical remission was defined as clinical remission at ≥4 of the 6 in-clinic assessment visits conducted during the Maintenance Phase at Weeks 24, 28, 32, 44, 56, and 66.

  9. Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those who Were Receiving Corticosteroids at Baseline [ Time Frame: Baseline and from Week 14 up to Week 66 ]
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Percentage of participants with clinical remission who will be off corticosteroids for at least 24 weeks prior to Week 66 will be reported.

  10. Maintenance Phase: Change from Baseline in CD-PRO/SS Score at Week 66 [ Time Frame: Baseline and Week 66 ]
  11. Overall Number of Participants who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) [ Time Frame: From Baseline up to Week 78 ]
  12. Overall Number of Participants with Adverse Events Leading to Study Drug Discontinuation [ Time Frame: From Baseline up to Week 78 ]
  13. Overall Number of Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  14. Overall Number of Participants who Experienced at Least One Infection-Related Serious Adverse Event [ Time Frame: From Baseline up to Week 78 ]
  15. Overall Number of Participants who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  16. Overall Number of Participants who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  17. Overall Number of Participants who Develop Malignancies [ Time Frame: From Baseline up to Week 78 ]
  18. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab [ Time Frame: Baseline, Pre-dose (Hour 0) on Weeks 4, 14, 24, 32, 44, 66 or early termination, 12 weeks after last dose (up to Week 78) ]
  19. Observed Trough Serum Concentration (Cmin) of Etrolizumab [ Time Frame: Pre-dose (Hour 0) at Baseline and Weeks 0, 10, 14, 16, 24, 28, 32, 44, and 66 or early termination (up to Week 66) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02394028


Contacts
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Contact: Reference Study ID Number: GA29144 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Show Show 604 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02394028    
Other Study ID Numbers: GA29144
2014-003824-36 ( EudraCT Number )
First Posted: March 20, 2015    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
rhuMAb Beta7
Gastrointestinal Agents
Immunologic Factors
Physiological Effects of Drugs