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Completed

NCT Number: NCT02394028

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

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.

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Key information

Conditions

Crohn Disease Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Italiano, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Etrolizumab

Drug

Etrolizumab will be administered as per regimen specified in individual arms.

Other names: RO5490261, RG7413

Placebo

Drug

Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.

Primary outcomes

  1. Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14

    Time frame: 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: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14

    Time frame: 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.

  3. Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14

    Time frame: Week 14

    Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.

  4. Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14

    Time frame: Week 14

    Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.

  5. 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.

    Maintenance phase participants were evaluated.

  6. Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66

    Time frame: Week 66

    Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Maintenance phase participants were evaluated.

Secondary outcomes

  1. Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6

    Time frame: 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: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6

    Time frame: 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.

  3. Induction Phase: Cohort 1: 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

    Endoscopic Remission is defined as SES-CD total score <=4 (<=2 for ileal only patients), with no segment having a subcategory score >1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.

  4. Induction Phase: Cohort 2 and 3: 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

    Endoscopic Remission is defined as SES-CD total score <=4 (<=2 for ileal only patients), with no segment having a subcategory score >1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.

  5. Induction Phase: Cohort 1: 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

    CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.

  6. Induction Phase: Cohort 2 and 3: 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

    CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.

  7. 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.

    Induction Phase Cohorts are not included

  8. 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.

    Induction Phase Cohorts are not included

  9. 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. Induction Phase Cohorts are not included

  10. 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

    Endoscopic Remission is defined as SES-CD total score <=4 (<=2 for ileal only patients), with no segment having a subcategory score >1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.

  11. 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. Induction Phase Cohorts are not included

  12. 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.

    Induction Phase Cohorts are not included

  13. Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66

    Time frame: Baseline and Week 66

    CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.

  14. 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

    Investigator text for AEs is coded using MedDRA version 24.0. For participants counts, multiple occurrences of AEs in the same category for an individual are counted only once. For event counts, multiple occurrences of AEs in the same category for an individual are counted separately. Severity Grades from 1 to 5.

  15. Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation

    Time frame: From Baseline up to Week 78

    Number of participants who discontinued the study due to the adverse events is reported.

  16. 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

    Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 are reported. Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = Death. The terms 'severe' and 'serious' are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs are counted only once per participant at the highest (worst) grade. Infections are identified by Primary System Organ Class term 'Infections and Infestations'

  17. Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event

    Time frame: From Baseline up to Week 78

    Investigator text for AEs is coded using MedDRA version 24.0. Infections are identified by primary System Organ Class term 'Infections and Infestations'. The terms 'severe' and 'serious' are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs in the same category for an individual are counted only once

  18. 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

    Investigator test for AEs is coding using MedDRA version 24.0. Injection-Site Reactions are identified by eCRF checkbox for local injection site reactions, and/or primary or secondary HLT Injection Site Reactions. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported.

  19. 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

    Investigator text for AEs is coded using MedDRA version 24.0. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported.

  20. Overall Number of Participants Who Develop Malignancies

    Time frame: From Baseline up to Week 78

    Participants with malignancies are reported. 'Malignancies are identified by SMQ Malignant and unspecified tumors (narrow)

  21. 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)

    Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result. Induction: treatment groups were pooled across cohorts 1-3. Maintenance: treatment group is stratified by induction dose

  22. Observed Trough Serum Concentration (Ctrough) of Etrolizumab

    Time frame: Induction Phase at Weeks 10 and 14, Maintenance Phase at Weeks 16, 24, 28, 32, 44, and 66

    Serum Etrolizumab Trough Concentration

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Acronym: BERGAMOT

Important dates

Study start
2015
Primary completion
2021
Study completion
2021
First posted
Mar 20, 2015
Registry last updated
Nov 16, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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