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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)

This study is currently recruiting participants.
Verified November 2017 by Hoffmann-La Roche
Sponsor:
ClinicalTrials.gov Identifier:
NCT02394028
First Posted: March 20, 2015
Last Update Posted: December 1, 2017
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.
Information provided by (Responsible Party):
Hoffmann-La Roche
  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 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.

Condition Intervention Phase
Crohn Disease Drug: Etrolizumab Drug: Placebo Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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) ]

Estimated Enrollment: 1150
Actual Study Start Date: March 20, 2015
Estimated Study Completion Date: June 30, 2019
Estimated Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
Drug: Etrolizumab
Etrolizumab will be administered as per regimen specified in individual arms.
Other Name: RO5490261
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.
Drug: Placebo
Etrolizumab matching placebo will be administered as per regimen specified in individual arms.
Experimental: Maintenance Phase: Etrolizumab 105 mg
Participants will receive SC injection of etrolizumab (105 mg every 4 weeks [Q4W]) during 52-week Maintenance Phase.
Drug: Etrolizumab
Etrolizumab will be administered as per regimen specified in individual arms.
Other Name: RO5490261
Placebo Comparator: Maintenance Phase: Placebo
Participants will receive SC injection of etrolizumab matching placebo (Q4W) during 52-week Maintenance Phase.
Drug: Placebo
Etrolizumab matching placebo will be administered as per regimen specified in individual arms.

  Eligibility

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.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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
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

  Show 511 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02394028     History of Changes
Other Study ID Numbers: GA29144
2014-003824-36 ( EudraCT Number )
First Submitted: February 27, 2015
First Posted: March 20, 2015
Last Update Posted: December 1, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases