Ulcerative Colitis
Conditions
Brief 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.
Interventions
DRUGEtrolizumab
105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.
DRUGInfliximab
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.
OTHERPlacebo (IV)
Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.
OTHERPlacebo (Injection)
Administered by SC injection Q4W until Week 52
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Number of Participants With Malignancies | 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 | 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 Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) | 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 | Baseline until the end of study (up to 66 weeks) | — |
| Number of Participants With Serious Infection-Related Adverse Events | 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 | 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 | 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 | Weeks 2, 10, 12, 30, and 54 | — |
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | 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 | Weeks 0, 4, 10, 12, 30, and 54 | — |
| 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 | 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. |
Countries
Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Netherlands, Norway, Portugal, Romania, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etrolizumab + Placebo (IV) Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46. | 199 |
| 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. | 198 |
| Total | 397 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 8 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 10 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-Compliance | 1 | 0 |
| Overall Study | Physician Decision | 5 | 4 |
| Overall Study | UC flare-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 11 |
Baseline characteristics
| Characteristic | Infliximab + Placebo (Injection) | Total | Etrolizumab + Placebo (IV) |
|---|---|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 13.4 | 39.8 years STANDARD_DEVIATION 14.3 | 40.0 years STANDARD_DEVIATION 15.2 |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS Both CS and IS | 30 Participants | 55 Participants | 25 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS Corticosteroids (CS) Alone | 56 Participants | 115 Participants | 59 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS Immunosuppressants (IS) Alone | 36 Participants | 76 Participants | 40 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS None | 76 Participants | 151 Participants | 75 Participants |
| Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline MCS ≥10 | 50 Participants | 110 Participants | 60 Participants |
| Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline MCS ≤9 | 147 Participants | 286 Participants | 139 Participants |
| Race/Ethnicity, Customized Asian | 30 Participants | 69 Participants | 39 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 19 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 158 Participants | 308 Participants | 150 Participants |
| Sex: Female, Male Female | 66 Participants | 147 Participants | 81 Participants |
| Sex: Female, Male Male | 132 Participants | 250 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 199 | 1 / 198 |
| other Total, other adverse events | 94 / 199 | 80 / 198 |
| serious Total, serious adverse events | 32 / 199 | 20 / 198 |
Outcome results
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)
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.
Time frame: Week 10, Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | 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 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS) | 19.7 percentage of participants |
p-value: 0.811495% CI: [-8.7, 6.83]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at 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.
Time frame: Weeks 10, 30, and 54
Population: Participants that completed the IBDQ Questionnaire at baseline and at the respective Time Points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab + Placebo (IV) | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | Week 10 | 43.2 scores on a scale | Standard Deviation 36.6 |
| Etrolizumab + Placebo (IV) | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | Week 30 | 53.5 scores on a scale | Standard Deviation 40.8 |
| Etrolizumab + Placebo (IV) | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | Week 54 | 58.2 scores on a scale | Standard Deviation 32.9 |
| Infliximab + Placebo (Injection) | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | Week 10 | 45.1 scores on a scale | Standard Deviation 39.4 |
| Infliximab + Placebo (Injection) | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | Week 30 | 59.6 scores on a scale | Standard Deviation 34.4 |
| Infliximab + Placebo (Injection) | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 | Week 54 | 63.2 scores on a scale | Standard Deviation 38.5 |
p-value: 0.410695% CI: [-10.6, 4.3]ANCOVA
p-value: 0.143495% CI: [-13.3, 1.9]ANCOVA
p-value: 0.110395% CI: [-13.6, 1.4]ANCOVA
Secondary
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 29 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 25 participants |
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)
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.
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrolizumab + Placebo (IV) | 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) | Grade 2 | 72 participants |
| Etrolizumab + Placebo (IV) | 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) | Grade 4 | 5 participants |
| Etrolizumab + Placebo (IV) | 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) | Grade 3 | 35 participants |
| Etrolizumab + Placebo (IV) | 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) | Grade 5 | 0 participants |
| Etrolizumab + Placebo (IV) | 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) | Grade 1 | 42 participants |
| Infliximab + Placebo (Injection) | 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) | Grade 5 | 1 participants |
| Infliximab + Placebo (Injection) | 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) | Grade 1 | 48 participants |
| Infliximab + Placebo (Injection) | 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) | Grade 2 | 74 participants |
| Infliximab + Placebo (Injection) | 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) | Grade 3 | 23 participants |
| Infliximab + Placebo (Injection) | 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) | Grade 4 | 5 participants |
Secondary
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
Time frame: Weeks 0, 4, 10, 12, 30, and 54
Population: A subset of etrolizumab-treated participants with at least one baseline or post-baseline ATA result from at least one sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | 69 participants |
Secondary
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0
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.
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 2 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 4 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 3 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 5 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 1 | 0 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 5 | 0 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 1 | 2 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 2 | 7 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 3 | 1 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 4 | 2 participants |
Secondary
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0
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.
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 2 | 31 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 4 | 2 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 3 | 8 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 5 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 1 | 28 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 5 | 0 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 1 | 27 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 2 | 29 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 3 | 4 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 | Grade 4 | 1 participants |
Secondary
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0
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.
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 2 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 4 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 3 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 5 | 0 participants |
| Etrolizumab + Placebo (IV) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 1 | 7 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 5 | 0 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 1 | 5 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 2 | 2 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 3 | 0 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 | Grade 4 | 0 participants |
Secondary
Number of Participants With Malignancies
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Malignancies | 3 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Malignancies | 1 participants |
Secondary
Number of Participants With Serious Infection-Related Adverse Events
Time frame: Baseline until the end of study (up to 66 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Number of Participants With Serious Infection-Related Adverse Events | 11 participants |
| Infliximab + Placebo (Injection) | Number of Participants With Serious Infection-Related Adverse Events | 3 participants |
Secondary
Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS
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.
Time frame: Week 10 and Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS | 10.6 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS | 13.1 percentage of participants |
p-value: 0.459195% CI: [-8.88, 4.14]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1
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.
Time frame: Week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1 | 20.6 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1 | 32.8 percentage of participants |
p-value: 0.129395% CI: [-20.5, -3.26]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS
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.
Time frame: Week 10 and Week 54
Population: Participants that achieved a Clinical Response at Week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | 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 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS | 33.3 percentage of participants |
p-value: 0.419695% CI: [-7.54, 18.13]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS
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.
Time frame: Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS | 20.1 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS | 23.7 percentage of participants |
p-value: 0.405695% CI: [-11.53, 4.74]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS
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.
Time frame: Week 10, Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS | 23.1 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS | 29.3 percentage of participants |
p-value: 0.172995% CI: [-14.51, 2.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS
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.
Time frame: Week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS | 49.2 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS | 59.1 percentage of participants |
p-value: 0.056495% CI: [-19.06, 0.29]Cochran-Mantel-Haenszel
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
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.
Time frame: Week 54
Population: Participants that were receiving corticosteroids at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | 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 percentage of participants |
| Infliximab + Placebo (Injection) | 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 | 17.4 percentage of participants |
p-value: 0.894195% CI: [-12.01, 10.68]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS
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.
Time frame: Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS | 17.6 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS | 22.7 percentage of participants |
p-value: 0.216895% CI: [-12.84, 2.94]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS
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.
Time frame: Baseline to Week 10, Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | 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 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS | 24.7 percentage of participants |
p-value: 0.123495% CI: [-14.3, 1.84]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS
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.
Time frame: Baseline to Week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS | 36.7 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS | 49.5 percentage of participants |
p-value: 0.011895% CI: [-21.84, -2.66]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS
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.
Time frame: Baseline to Week 54
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrolizumab + Placebo (IV) | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS | 27.1 percentage of participants |
| Infliximab + Placebo (Injection) | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS | 32.3 percentage of participants |
p-value: 0.284595% CI: [-13.76, 4.12]Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics: Etrolizumab Serum Concentration
Time frame: Weeks 2, 10, 12, 30, and 54
Population: A subset of etrolizumab-treated participants who received at least one dose of study drug and had at least one quantifiable concentration measured post baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab + Placebo (IV) | Pharmacokinetics: Etrolizumab Serum Concentration | Week 32 | 13.9 microgram/milliliter | Standard Deviation 5.96 |
| Etrolizumab + Placebo (IV) | Pharmacokinetics: Etrolizumab Serum Concentration | Week 54 | 13.2 microgram/milliliter | Standard Deviation 5.68 |
| Etrolizumab + Placebo (IV) | Pharmacokinetics: Etrolizumab Serum Concentration | Week 2 | 7.64 microgram/milliliter | Standard Deviation 2.75 |
| Etrolizumab + Placebo (IV) | Pharmacokinetics: Etrolizumab Serum Concentration | Week 10 | 12.0 microgram/milliliter | Standard Deviation 4.63 |
| Etrolizumab + Placebo (IV) | Pharmacokinetics: Etrolizumab Serum Concentration | Week 12 | 6.92 microgram/milliliter | Standard Deviation 3.18 |