Phase 3
Completed N=609
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
Source: ClinicalTrials.gov NCT02100696 ↗Enrolled (actual)
609
Serious AEs
6.5%
Results posted
Jun 2021
Primary outcomePrimary: Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) — 6.3; 18.5 Percentage of Participants — p=0.0033
◆ Published Evidence
Established
92citations · ~23 / year
Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial.
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.
Linked Publications (3)
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Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial.
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Etrolizumab for the Treatment of Ulcerative Colitis and Crohn's Disease: An Overview of the Phase 3 Clinical Program.
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Impact of missing patient report outcomes in clinical trials for ulcerative colitis: Should we always assume treatment failure?
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) |
6.3; 18.5 | 0.0033 sig |
| PRIMARY 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 |
20.2; 24.1 | 0.4956 |
| SECONDARY Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS |
6.3; 18.8 | 0.0028 sig |
| SECONDARY Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS |
31.6; 45.8 | 0.0241 sig |
| SECONDARY 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 |
25.3; 33.3 | 0.1605 |
| SECONDARY Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore |
9.5; 17.2 | 0.3881 |
| SECONDARY Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index |
25.0; 29.7 | 0.5879 |
| SECONDARY Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore |
-0.4; -0.7 | 0.0351 sig |
| SECONDARY Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore |
-0.5; -0.6 | 0.2698 |
| SECONDARY 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 |
-3.6; -5.2 | 0.2698 |
| SECONDARY Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire |
-1.1; -1.5 | 0.3881 |
| SECONDARY 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) |
28.4; 37.4 | 0.0445 sig |
| SECONDARY 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 |
36.4; 38.1 | 0.9959 |
| SECONDARY Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS |
21.1; 25.0 | 0.5014 |
| SECONDARY Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS |
34.1; 36.6 | 0.9538 |
| SECONDARY 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 |
21.1; 35.7 | 0.0153 sig |
| SECONDARY Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index |
14.1; 30.8 | 0.0073 sig |
| SECONDARY Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore |
11.4; 23.2 | 0.0174 sig |
| SECONDARY 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 |
12.7; 20.4 | 0.3015 |
| SECONDARY 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 |
10.9; 18.5 | 0.2787 |
| SECONDARY Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire |
-6.3; -7.8 | 0.0763 |
| SECONDARY Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire |
-1.8; -2.0 | 0.5329 |
| SECONDARY Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ |
57.2; 52.3 | 0.2228 |
| SECONDARY 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) |
39; 31; 117; 8; 19; 33 | — |
| SECONDARY Number of Participants With Adverse Events Leading to Study Drug Discontinuation |
2; 1; 12; 4; 9; 10 | — |
| SECONDARY Number of Participants With Serious Infection-Related Adverse Events |
2; 1; 5; 0; 3; 3 | — |
| SECONDARY Number of Participants With Infection-Related Adverse Events |
38; 29; 100; 13; 44; 58 | — |
| SECONDARY Number of Participants With Injection-Site Reaction-Related Adverse Events |
7; 5; 4; 2; 2; 8 | — |
| SECONDARY Number of Participants With Hypersensitivity Reaction-Related Adverse Events |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Malignancies |
0; 0; 2; 0; 0; 2 | — |
| SECONDARY Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study |
9; 2; 6; 68; 35; 28 | — |
| SECONDARY Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) |
11.0; 12.7; 14.0; 0.474; 9.55; 10.7 | — |
| SECONDARY Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ) |
0.0400; 0.0400 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT02100696) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.