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A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors (HICKORY)

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ClinicalTrials.gov Identifier: NCT02100696
Recruitment Status : Active, not recruiting
First Posted : April 1, 2014
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 27, 2014
First Posted Date  ICMJE April 1, 2014
Last Update Posted Date July 23, 2019
Actual Study Start Date  ICMJE May 21, 2014
Estimated Primary Completion Date April 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Induction Phase: Percentage of Participants with Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) [ Time Frame: Week 14 ]
  • Maintenance Phase: Percentage of Participants with Remission at Week 66 Among Participants Who Had Achieved a Clinical Response at Week 14, as Determined by the MCS [ Time Frame: Week 66 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
  • Remission as determined by the Mayo Clinic Score (MCS) [ Time Frame: At Week 14 ]
  • Remission maintenance among patients with remission at Week 14. Measured by MCS [ Time Frame: At Week 66 ]
Change History Complete list of historical versions of study NCT02100696 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Induction Phase: Percentage of Participants with Clinical Remission at Week 14, as Determined by the MCS [ Time Frame: Week 14 ]
  • Induction Phase: Percentage of Participants with Clinical Response at Week 14, as Determined by the MCS [ Time Frame: Week 14 ]
  • Induction Phase: Percentage of Participants with Improvement from Baseline in Endoscopic Appearance of the Mucosa at Week 14, as Determined by the MCS Endoscopic Subscore [ Time Frame: Baseline and Week 14 ]
  • Induction Phase: Percentage of Participants with Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore [ Time Frame: Week 14 ]
  • Induction Phase: Percentage of Participants with Histologic Remission at Week 14, as Determined by the Nancy Histological Index [ Time Frame: Week 14 ]
  • Induction Phase: Change from Baseline to Week 6 in MCS Rectal Bleed Subscore [ Time Frame: Baseline and Week 6 ]
  • Induction Phase: Change from Baseline to Week 6 in MCS Stool Frequency Subscore [ Time Frame: Baseline and Week 6 ]
  • Induction Phase: Change from Baseline to Week 14 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire [ Time Frame: Baseline and Week 14 ]
  • Induction Phase: Change from Baseline to Week 14 in UC Abdominal Symptoms, as Assessed by the UC-PRO/SS Questionnaire [ Time Frame: Baseline and Week 14 ]
  • Induction Phase: Change from Baseline to Week 14 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline and Week 14 ]
  • Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66 Among Participants Who Had Achieved Clinical Remission at Week 14, as Determined by the MCS [ Time Frame: Week 66 ]
  • Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66, as Determined by the MCS [ Time Frame: Week 66 ]
  • Maintenance Phase: Percentage of Participants with Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS [ Time Frame: Week 66 ]
  • Maintenance Phase: Percentage of Participants with Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 66, as Determined by the MCS Endoscopic Subscore [ Time Frame: Baseline and Week 66 ]
  • Maintenance Phase: Percentage of Participants with Histologic Remission at Week 66, as Determined by the Nancy Histological Index [ Time Frame: Week 66 ]
  • Maintenance Phase: Percentage of Participants with Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore [ Time Frame: Week 66 ]
  • Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [ Time Frame: Week 66 ]
  • Maintenance Phase: Percentage of Participants with Corticosteroid-Free Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [ Time Frame: Week 66 ]
  • Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire [ Time Frame: Baseline and Week 66 ]
  • Maintenance Phase: Change From Baseline to Week 66 in UC Abdominal Symptoms, as Assessed by the UC-PRO/SS Questionnaire [ Time Frame: Baseline and Week 66 ]
  • Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ [ Time Frame: Baseline and Week 66 ]
  • Number of Participants with 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 ]
  • Number of Participants with Adverse Events Leading to Study Drug Discontinuation [ Time Frame: From Baseline up to Week 78 ]
  • Number of Participants with Serious Infection-Related Adverse Events [ Time Frame: From Baseline up to Week 78 ]
  • Number of Participants with Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  • Number of Participants with Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  • Number of Participants with Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  • Number of Participants with Malignancies [ Time Frame: From Baseline up to Week 78 ]
  • Number of Participants with Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study [ Time Frame: Pre-dose at Baseline, Weeks 4, 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78) ]
  • Etrolizumab Serum Trough Concentration [ Time Frame: Pre-dose at Baseline, Weeks 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
Clinical remission as determined by MCS [ Time Frame: At Weeks 14 and 66 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors
Official Title  ICMJE Phase III, Double-Blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Etrolizumab During Induction and Maintenance in Patients With Moderate to Severe Active Ulcerative Colitis Who Have Been Previously Exposed to TNF Inhibitors
Brief Summary This Phase III, double-blind, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab during induction and maintenance of remission compared with placebo in the treatment of participants with moderately to severely active ulcerative colitis (UC) who have been previously exposed to TNF inhibitors.
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 Ulcerative Colitis
Intervention  ICMJE
  • Drug: Etrozulimab
    Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
    Other Names:
    • PRO145223
    • RO5490261
    • RG7413
  • Drug: Placebo
    Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
Study Arms  ICMJE
  • Experimental: Cohort 1: Etrolizumab (Open-Label Induction Phase)
    Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase.
    Intervention: Drug: Etrozulimab
  • Experimental: Cohort 2: Etrolizumab (Double-Blind Induction Phase)
    Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
    Intervention: Drug: Etrozulimab
  • Placebo Comparator: Cohort 2: Placebo (Double-Blind Induction Phase)
    Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
    Intervention: Drug: Placebo
  • Experimental: Etrolizumab Responders: Etrolizumab (Maintenance Phase)
    Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
    Intervention: Drug: Etrozulimab
  • Placebo Comparator: Etrolizumab Responders: Placebo (Maintenance Phase)
    Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
    Intervention: Drug: Placebo
  • Placebo Comparator: Placebo Responders: Placebo (Maintenance Phase)
    Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the 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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 24, 2019)
609
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2014)
800
Estimated Study Completion Date  ICMJE July 17, 2020
Estimated Primary Completion Date April 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of UC established at least 3 months prior to Day 1
  • Moderately to severely active UC as determined by the Mayo Clinic Score (MCS) assessment
  • Treatment within 5 years prior to screening with one or two induction regimens that contain TNF inhibitors (including TNF inhibitor biosimilars)
  • Washout of anti-TNF therapy for at least 8 weeks preceding Day 1
  • Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
  • Use of highly effective contraception as defined by the protocol
  • Must have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening

Exclusion Criteria:

  • A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic colitis, radiation colitis, or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps
  • Prior or planned surgery for UC
  • Past or present ileostomy or colostomy
  • Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab)
  • Any prior treatment with anti-adhesion molecules (e.g. anti-MAdCAM-1)
  • Any prior treatment with rituximab
  • Any treatment with tofacitinib during screening
  • Congenital or acquired immune deficiency, chronic hepatitis B or C infection, human immunodeficiency virus (HIV) positive, or history of tuberculosis (active or latent)
  • Evidence of or treatment for Clostridium difficile or clinically significant cytomegalovirus (CMV) colitis within 60 days prior to Day 1
  • Evidence of or treatment for other intestinal pathogens within 30 days prior to Day 1
  • History of recurrent opportunistic infections and/or severe disseminated viral infections
  • History of organ transplant
  • Any major episode of infection requiring treatment with intravenous (IV) antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
  • Received a live attenuated vaccine within 4 weeks prior to Day 1
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Czechia,   Denmark,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Korea, Republic of,   Lithuania,   Mexico,   Netherlands,   Poland,   Romania,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries Czech Republic,   New Zealand
 
Administrative Information
NCT Number  ICMJE NCT02100696
Other Study ID Numbers  ICMJE GA28950
2013-004278-88 ( 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 July 2019

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