Phase 3
Completed N=397
A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors
Source: ClinicalTrials.gov NCT02136069 ↗Enrolled (actual)
397
Serious AEs
13.1%
Results posted
Aug 2021
Primary outcomePrimary: Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS) — 18.6; 19.7 percentage of participants — p=0.8114
◆ Published Evidence
Established
93citations · ~23 / year
Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study.
Summary
This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then once every 8 weeks [Q8W]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.
Linked Publications (2)
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Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study.
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Etrolizumab for the Treatment of Ulcerative Colitis and Crohn's Disease: An Overview of the Phase 3 Clinical Program.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS) |
18.6; 19.7 | 0.8114 |
| SECONDARY Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1 |
20.6; 32.8 | 0.1293 |
| SECONDARY Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS |
20.1; 23.7 | 0.4056 |
| SECONDARY Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS |
10.6; 13.1 | 0.4591 |
| SECONDARY Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS |
37.8; 33.3 | 0.4196 |
| SECONDARY Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS |
36.7; 49.5 | 0.0118 sig |
| SECONDARY Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS |
27.1; 32.3 | 0.2845 |
| SECONDARY Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS |
18.1; 24.7 | 0.1234 |
| SECONDARY Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS |
17.6; 22.7 | 0.2168 |
| SECONDARY Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS |
49.2; 59.1 | 0.0564 |
| SECONDARY Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS |
23.1; 29.3 | 0.1729 |
| SECONDARY Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS |
15.5; 17.4 | 0.8941 |
| SECONDARY Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) |
42; 48; 72; 74; 35; 23 | — |
| SECONDARY Number of Participants With Adverse Events Leading to Study Drug Discontinuation |
29; 25 | — |
| SECONDARY Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 |
28; 27; 31; 29; 8; 4 | — |
| SECONDARY Number of Participants With Serious Infection-Related Adverse Events |
11; 3 | — |
| SECONDARY Number of Participants With Malignancies |
3; 1 | — |
| SECONDARY Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 |
7; 5; 0; 2; 0; 0 | — |
| SECONDARY Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 |
0; 2; 0; 7; 0; 1 | — |
| SECONDARY Pharmacokinetics: Etrolizumab Serum Concentration |
7.64; 12.0; 6.92; 13.9; 13.2 | — |
| SECONDARY Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 |
43.2; 45.1; 53.5; 59.6; 58.2; 63.2 | 0.4106 |
| SECONDARY Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab |
69 | — |
Eligibility Criteria
Inclusion Criteria
- Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
- Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)
- An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
- Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
- Use of highly effective contraception during and at least 24 weeks after the last dose of study drug
Exclusion Criteria
- A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation 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
- Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, efalizumab, and tofactinib)
- History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients
- Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)
Data sourced from ClinicalTrials.gov (NCT02136069) 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.