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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02100696
• Date of registration: 27/03/2014
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: 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
• Scientific 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
• Date of first enrolment: May 21, 2014
• Target sample size: 609
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02100696
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, New Zealand, Poland, Romania, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: Etrozulimab

Drug: Placebo

Primary Outcome(s)

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]

Secondary Outcome(s)

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 Adverse Events Leading to Study Drug Discontinuation [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 Serious Infection-Related Adverse Events [Time Frame: From Baseline up to Week 78]

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: Percentage of Participants with Clinical Response at Week 14, as Determined by the MCS [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]

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 Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS [Time Frame: Week 66]

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]

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]

Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66, as Determined by the MCS [Time Frame: 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]

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: Change From Baseline to Week 66 in UC Abdominal Symptoms, as Assessed by the UC-PRO/SS Questionnaire [Time Frame: Baseline and Week 66]

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)]

Induction Phase: Change from Baseline to Week 6 in MCS Rectal Bleed Subscore [Time Frame: Baseline and Week 6]

Induction Phase: Percentage of Participants with Clinical Remission at Week 14, as Determined by the MCS [Time Frame: Week 14]

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]

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)]

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 Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0 [Time Frame: From Baseline up to Week 78]

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 6 in MCS Stool Frequency Subscore [Time Frame: Baseline and Week 6]

Maintenance Phase: Percentage of Participants with Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore [Time Frame: Week 66]

Induction Phase: Percentage of Participants with Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore [Time Frame: Week 14]

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: 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 Corticosteroid-Free Clinical Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [Time Frame: Week 66]

Number of Participants with Malignancies [Time Frame: From Baseline up to Week 78]

Secondary ID(s)

GA28950

2013-004278-88

Source(s) of Monetary Support

Please refer to primary and secondary sponsors