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 (GARDENIA)
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| ClinicalTrials.gov Identifier: NCT02136069 |
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Recruitment Status :
Completed
First Posted : May 12, 2014
Results First Posted : August 13, 2021
Last Update Posted : December 3, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ulcerative Colitis | Drug: Etrolizumab Drug: Infliximab Other: Placebo (IV) Other: Placebo (Injection) | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 397 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study to Evaluate the Efficacy and Safety of Etrolizumab Compared With Infliximab in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors |
| Actual Study Start Date : | December 24, 2014 |
| Actual Primary Completion Date : | June 23, 2020 |
| Actual Study Completion Date : | June 23, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Etrolizumab + Placebo (IV)
Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
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Drug: Etrolizumab
105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.
Other Names:
Other: Placebo (IV) Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46. |
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Active Comparator: Infliximab + Placebo (Injection)
Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
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Drug: Infliximab
5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46. Other: Placebo (Injection) Administered by SC injection Q4W until Week 52 |
- Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS) [ Time Frame: Week 10, Week 54 ]
Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Clinical Remission is MCS ≤2 with individual subscores ≤1.
- Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1 [ Time Frame: Week 10 ]MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
- Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS [ Time Frame: Week 54 ]
Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Remission is MCS ≤2 with individual subscores ≤1.
- Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS [ Time Frame: Week 10 and Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Remission is MCS ≤2 with individual subscores ≤1.
- Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS [ Time Frame: Week 10 and Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Remission is MCS ≤2 with individual subscores ≤1.
Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
- Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS [ Time Frame: Baseline to Week 10 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
- Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS [ Time Frame: Baseline to Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
- Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS [ Time Frame: Baseline to Week 10, Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
- Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS [ Time Frame: Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Endoscopic Remission is Endoscopy subscore = 0.
- Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS [ Time Frame: Week 10 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
- Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS [ Time Frame: Week 10, Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
- 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 [ Time Frame: Week 54 ]
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Clinical Remission is MCS ≤2 with individual subscores ≤1.
- 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) [ Time Frame: Baseline until the end of study (up to 66 weeks) ]All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
- Number of Participants With Adverse Events Leading to Study Drug Discontinuation [ Time Frame: Baseline until the end of study (up to 66 weeks) ]
- Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 [ Time Frame: Baseline until the end of study (up to 66 weeks) ]All AEs were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
- Number of Participants With Serious Infection-Related Adverse Events [ Time Frame: Baseline until the end of study (up to 66 weeks) ]
- Number of Participants With Malignancies [ Time Frame: Baseline until the end of study (up to 66 weeks) ]
- Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 [ Time Frame: Baseline until the end of study (up to 66 weeks) ]All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
- Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 [ Time Frame: Baseline until the end of study (up to 66 weeks) ]All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
- Pharmacokinetics: Etrolizumab Serum Concentration [ Time Frame: Weeks 2, 10, 12, 30, and 54 ]
- Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 [ Time Frame: Weeks 10, 30, and 54 ]
The IBDQ is used to assess participant's health-related quality of life (QOL). The 32-item questionnaire contains four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale with a higher score indicating better health-related QOL.
IBDQ score is a total score summed up from across all 32 questions on the questionnaire. The score can range from 32-224 and the higher score indicates a better quality of life.
- Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab [ Time Frame: Weeks 0, 4, 10, 12, 30, and 54 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
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): NCT02136069
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| Study Director: | Clinical Trials | Hoffmann-La Roche |
Documents provided by Hoffmann-La Roche:
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT02136069 |
| Other Study ID Numbers: |
GA29103 2013-004282-14 ( EudraCT Number ) |
| First Posted: | May 12, 2014 Key Record Dates |
| Results First Posted: | August 13, 2021 |
| Last Update Posted: | December 3, 2021 |
| Last Verified: | December 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Colitis Colitis, Ulcerative Ulcer Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Colonic Diseases Intestinal Diseases Pathologic Processes |
Inflammatory Bowel Diseases Infliximab Etrolizumab Dermatologic Agents Gastrointestinal Agents Antirheumatic Agents Immunologic Factors Physiological Effects of Drugs |