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

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ClinicalTrials.gov Identifier: NCT02394028
Recruitment Status : Recruiting
First Posted : March 20, 2015
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE February 27, 2015
First Posted Date  ICMJE March 20, 2015
Last Update Posted Date October 29, 2019
Actual Study Start Date  ICMJE March 20, 2015
Estimated Primary Completion Date June 4, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • Induction Phase: 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 (AP) mean daily score </=1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
  • Induction Phase: 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.
  • Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66 [ Time Frame: Week 66 ]
    Clinical remission is defined as SF mean daily score </=3 and AP mean daily score </=1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
  • Maintenance of clinical remission (as determined by PRO2 score) at Week 66 (US) [ Time Frame: At Week 66 ]
  • Induction Phase: Clinical remission as determined by the Crohn's Disease Activity Index (CDAI) score (ex-US) [ Time Frame: At Week 14 ]
  • Maintenance of clinical remission (as determined by CDAI score) after at least 52 weeks and corticosteroid-free for at least 52 weeks (ex-US) [ Time Frame: 52 weeks ]
  • Induction Phase: Clinical remission as determined by the 2 Item Patient Reported Outcome (PRO2) score (US) [ Time Frame: At Week 14 ]
Change History Complete list of historical versions of study NCT02394028 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • Induction Phase: Percentage of Participants with Clinical Remission at Week 6 [ Time Frame: Week 6 ]
    Clinical remission is defined as SF mean daily score </=3 and AP mean daily score </=1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
  • 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 ]
  • 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 ]
  • Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66 Among Participants who Achieved Clinical Remission at Week 14 [ Time Frame: Weeks 14 and 66 ]
    Clinical remission is defined as SF mean daily score </=3 and AP mean daily score </=1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
  • Maintenance Phase: Percentage of Participants with CS-Free Clinical Remission at Week 66 [ Time Frame: Week 66 ]
    Clinical remission is defined as SF mean daily score </=3 and AP mean daily score </=1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
  • Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66 Among Participants who Achieved Endoscopic Improvement at Week 14 [ Time Frame: Weeks 14 and 66 ]
    Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score.
  • 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 ]
  • 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 AP 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.
  • Maintenance Phase: Percentage of Participants with CS-Free Clinical Remission for at Least 24 Weeks at Week 66 [ Time Frame: Week 14 up to Week 66 ]
    Clinical remission is defined as SF mean daily score </=3 and AP 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-CS for at least 24 weeks prior to Week 66 will be reported.
  • Maintenance Phase: Change from Baseline in CD-PRO/SS Score at Week 66 [ Time Frame: Baseline and Week 66 ]
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to Week 78 ]
  • 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) ]
  • Etrolizumab Serum Concentrations [ Time Frame: Pre-dose (Hour 0) at Weeks 14 and 66 ]
  • Observed Trough Serum Concentration (Cmin) of Etrolizumab [ Time Frame: Pre-dose (Hour 0) at Weeks 16, 24, 28, 32, 44, and 66 or early termination (up to Week 66) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
  • Safety (composite outcome measure): Incidence and severity of adverse events; incidence of anti-therapeutic antibodies to etrolizumab [ Time Frame: Up to 90 weeks ]
  • Proportion of patients who achieve 100 points reduction in their CDAI score (CDAI-100 response) [ Time Frame: At Week 14 ]
  • Maintenance Phase: Proportion of patients who achieve CDAI-100 response [ Time Frame: At Week 66 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Whether Etrolizumab is a Safe and Effective Treatment for Participants With Moderately to Severely Active Crohn's Disease (CD)
Official Title  ICMJE 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
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 moderate to severely active CD in participants who are refractory or intolerant to corticosteroids (CS), immunosuppressants (IS), or anti-tumor necrosis factors (anti-TNFs) or have inadequate response to anti-tumor necrosis factor (TNF-IR). Participants who enroll on the basis of refractory or intolerance to CS and/or IS may have been previously exposed to anti-TNFs or be naïve to anti-TNFs. The study period will consist of Screening Phase (up to 35 days) plus (+) 14-week Induction Phase + 52-week Maintenance Phase + 12-week Safety Follow-up Phase. At Week 14 (end of Induction Phase), participants achieving decrease of 70 points in Crohn's Disease Activity Index (CDAI) from baseline (CDAI-70 response) without the use of rescue therapy will continue to the Maintenance Phase.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Crohn Disease
Intervention  ICMJE
  • Drug: Etrolizumab
    Etrolizumab will be administered as per regimen specified in individual arms.
    Other Name: RO5490261
  • Drug: Placebo
    Etrolizumab matching placebo will be administered as per regimen specified in individual arms.
Study Arms  ICMJE
  • Experimental: Induction Phase: Etrolizumab 105 Milligrams (mg)
    Participants will receive subcutaneous (SC) injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and etrolizumab matching placebo at Week 2 during 14-week Induction Phase.
    Interventions:
    • Drug: Etrolizumab
    • Drug: Placebo
  • Experimental: Induction Phase: Etrolizumab 210 mg
    Participants will receive SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during 14-week Induction Phase.
    Intervention: Drug: Etrolizumab
  • Placebo Comparator: Induction Phase: Placebo
    Participants will receive SC injection of etrolizumab matching placebo at Weeks 0, 2, 4, 8 and 12 during 14-week Induction Phase.
    Intervention: Drug: Placebo
  • Experimental: Maintenance Phase: Etrolizumab 105 mg
    Participants will receive SC injection of etrolizumab (105 mg every 4 weeks [Q4W]) during 52-week Maintenance Phase.
    Intervention: Drug: Etrolizumab
  • Placebo Comparator: Maintenance Phase: Placebo
    Participants will receive SC injection of etrolizumab matching placebo (Q4W) during 52-week Maintenance Phase.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2017)
1150
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2015)
1250
Estimated Study Completion Date  ICMJE August 27, 2021
Estimated Primary Completion Date June 4, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Moderately to severely active 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 CS, 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Croatia,   Czechia,   Estonia,   France,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Mexico,   Netherlands,   New Zealand,   Poland,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02394028
Other Study ID Numbers  ICMJE GA29144
2014-003824-36 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP