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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 : Completed
First Posted : April 1, 2014
Last Update Posted : May 8, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: Etrozulimab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 609 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 21, 2014
Actual Primary Completion Date : April 16, 2020
Actual Study Completion Date : April 16, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: Etrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
Other Names:
  • PRO145223
  • RO5490261
  • RG7413
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.
 Drug: Etrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
Other Names:
  • PRO145223
  • RO5490261
  • RG7413
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.
 Drug: Placebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
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.
 Drug: Etrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
Other Names:
  • PRO145223
  • RO5490261
  • RG7413
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.
 Drug: Placebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
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.
 Drug: Placebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.


Outcome Measures
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Primary Outcome Measures :
  1. Induction Phase: Percentage of Participants with Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) [ Time Frame: Week 14 ]
  2. 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 ]

Secondary Outcome Measures :
  1. Induction Phase: Percentage of Participants with Clinical Remission at Week 14, as Determined by the MCS [ Time Frame: Week 14 ]
  2. Induction Phase: Percentage of Participants with Clinical Response at Week 14, as Determined by the MCS [ Time Frame: Week 14 ]
  3. 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 ]
  4. Induction Phase: Percentage of Participants with Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore [ Time Frame: Week 14 ]
  5. Induction Phase: Percentage of Participants with Histologic Remission at Week 14, as Determined by the Nancy Histological Index [ Time Frame: Week 14 ]
  6. Induction Phase: Change from Baseline to Week 6 in MCS Rectal Bleed Subscore [ Time Frame: Baseline and Week 6 ]
  7. Induction Phase: Change from Baseline to Week 6 in MCS Stool Frequency Subscore [ Time Frame: Baseline and Week 6 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66, as Determined by the MCS [ Time Frame: Week 66 ]
  13. 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 ]
  14. 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 ]
  15. Maintenance Phase: Percentage of Participants with Histologic Remission at Week 66, as Determined by the Nancy Histological Index [ Time Frame: Week 66 ]
  16. Maintenance Phase: Percentage of Participants with Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore [ Time Frame: Week 66 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]
  22. 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 ]
  23. Number of Participants with Adverse Events Leading to Study Drug Discontinuation [ Time Frame: From Baseline up to Week 78 ]
  24. Number of Participants with Serious Infection-Related Adverse Events [ Time Frame: From Baseline up to Week 78 ]
  25. Number of Participants with Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  26. Number of Participants with Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  27. Number of Participants with Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 78 ]
  28. Number of Participants with Malignancies [ Time Frame: From Baseline up to Week 78 ]
  29. 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) ]
  30. 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) ]

Eligibility Criteria
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Information from the National Library of Medicine

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

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
Contacts and Locations
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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): NCT02100696


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02100696    
Other Study ID Numbers: GA28950
2013-004278-88 ( EudraCT Number )
First Posted: April 1, 2014    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: May 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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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
 Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
rhuMAb Beta7
Gastrointestinal Agents
Immunologic Factors
Physiological Effects of Drugs