Ulcerative Colitis
Conditions
Brief 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.
Interventions
DRUGEtrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
DRUGPlacebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) | Week 14 | The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. |
| 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 | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS | Week 14 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Clinical Remission is MCS ≤2 with individual subscores ≤1. |
| Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS | Week 14 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. 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. |
| 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 | Baseline and Week 14 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1. |
| Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore | Week 14 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0. |
| Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index | Week 14 | Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1. |
| Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore | Baseline and Week 6 | Rectal bleeding data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = no blood in the stool; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed. The Mayo Clinic Score (MCS) rectal bleeding subscore was calculated as the worst value of three days of daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline rectal bleeding (RB) subscore. |
| Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore | Baseline and Week 6 | Stool frequency data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = normal number of stools; 1 = 1 to 2 more stools than normal; 2 = 3 to 4 more stools than normal; 3 = 5 or more stools than normal. The Mayo Clinic Score (MCS) stool frequency subscore was calculated as the average of three days daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline stool frequency (SF) subscore. |
| 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 | Baseline and Week 14 | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. |
| Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire | Baseline and Week 14 | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. |
| 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) | Baseline and Week 14 | The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. |
| 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 | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1. |
| Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1. |
| Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. |
| 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 | Baseline and Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1. |
| Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index | Week 66 | Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1. |
| Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0. |
| 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 | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66. |
| 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 | Week 66 | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66. |
| Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire | Baseline and Week 66 | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. |
| Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire | Baseline and Week 66 | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. |
| Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ | Baseline and Week 66 | The IBDQ is used to assess participant's health-related quality of life (QOL). The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. |
| 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) | From Baseline up to Week 78 | 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 | From Baseline up to Week 78 | — |
| Number of Participants With Serious Infection-Related Adverse Events | From Baseline up to Week 78 | — |
| Number of Participants With Infection-Related Adverse Events | From Baseline up to Week 78 | 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. 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 Injection-Site Reaction-Related Adverse Events | From Baseline up to Week 78 | — |
| Number of Participants With Hypersensitivity Reaction-Related Adverse Events | From Baseline up to Week 78 | — |
| Number of Participants With Malignancies | From Baseline up to Week 78 | — |
| Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Pre-dose at Baseline, Weeks 4, 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78) | A tiered strategy was used to detect and characterize etrolizumab antibodies within this clinical study. When determining post baseline incidence, participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following etrolizumab drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were ADA negative or had missing data at baseline and all post baseline samples were negative, or if they were ADA positive at baseline but did not have any post baseline samples with a titer that was at least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected). |
| Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Pre-dose (0 hour) at Baseline and Weeks 14, 24, 44 and 66 | As per Protocol, the timepoints for each arm where more than a third of the samples were above the lower limit of quantification (LLOQ), full summary statistics (Mean and Standard Deviation) were reported. For timepoints below the LLOQ, only the Median and Max were reported as a separate outcome measure below. |
| Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ) | Weeks 44 and 66 | As per Protocol, the timepoints for each arm where more than a third of the samples were below the LLOQ only the Median and Max were reported. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Lithuania, Mexico, Netherlands, Poland, Romania, South Korea, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 184 centers in 24 countries.
Pre-assignment details
A total of 609 participants were enrolled into the Induction phase of this study and the entire study. A subset (259) of these participants moved into the Maintenance phase of this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | 130 |
| Cohort 2: Placebo (Double-Blind Induction Phase) Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | 95 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | 384 |
| Placebo Responders: Placebo (Maintenance Phase) Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | 27 |
| Etrolizumab Responders: Placebo (Maintenance Phase) Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | 115 |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. | 117 |
| Total | 868 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Induction Phase | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Induction Phase | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 |
| Induction Phase | Multiple Reasons | 5 | 2 | 8 | 0 | 0 | 0 |
| Induction Phase | Physician Decision | 1 | 0 | 2 | 0 | 0 | 0 |
| Induction Phase | Protocol Violation | 0 | 1 | 1 | 0 | 0 | 0 |
| Induction Phase | Withdrawal by Subject | 8 | 2 | 13 | 0 | 0 | 0 |
| Maintenance Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 |
| Maintenance Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Phase | Multiple Reasons | 0 | 0 | 0 | 0 | 2 | 1 |
| Maintenance Phase | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Phase | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Phase | Withdrawal by Subject | 0 | 0 | 0 | 1 | 4 | 2 |
Baseline characteristics
| Characteristic | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Total | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 13.8 | 42.0 years STANDARD_DEVIATION 13.5 | 40.0 years STANDARD_DEVIATION 12.9 | 40.1 years STANDARD_DEVIATION 13.4 | 40.7 years STANDARD_DEVIATION 13.3 | 38.8 years STANDARD_DEVIATION 13.9 | 39.5 years STANDARD_DEVIATION 13.5 |
| Race/Ethnicity, Customized American Indian or Alaska Native | — | — | — | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 5 Participants | 5 Participants | 37 Participants | 26 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 8 Participants | 9 Participants | 39 Participants | 30 Participants | 5 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 21 Participants | 95 Participants | 94 Participants | 515 Participants | 321 Participants | 76 Participants | 118 Participants |
| Race/Ethnicity, Customized Not Reported or Unknown | 5 Participants | 12 Participants | 14 Participants | 31 Participants | 33 Participants | 14 Participants | 8 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 13 Participants | 17 Participants | 35 Participants | 48 Participants | 15 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 96 Participants | 92 Participants | 208 Participants | 304 Participants | 73 Participants | 109 Participants |
| Sex: Female, Male Female | 9 Participants | 43 Participants | 57 Participants | 109 Participants | 160 Participants | 41 Participants | 52 Participants |
| Sex: Female, Male Male | 18 Participants | 72 Participants | 60 Participants | 356 Participants | 224 Participants | 54 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 130 | 0 / 95 | 0 / 384 | 0 / 27 | 0 / 114 | 0 / 112 |
| other Total, other adverse events | 38 / 130 | 31 / 95 | 115 / 384 | 20 / 27 | 78 / 114 | 78 / 112 |
| serious Total, serious adverse events | 11 / 130 | 5 / 95 | 20 / 384 | 2 / 27 | 7 / 114 | 11 / 112 |
Outcome results
Primary
Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS)
The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0.
Time frame: Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) | 6.3 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) | 18.5 Percentage of Participants |
p-value: 0.003395% CI: [3.95, 17.67]Cochran-Mantel-Haenszel
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. 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 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | 24.1 Percentage of Participants |
p-value: 0.495695% CI: [-7.13, 14.56]Cochran-Mantel-Haenszel
Secondary
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
As per Protocol, the timepoints for each arm where more than a third of the samples were above the lower limit of quantification (LLOQ), full summary statistics (Mean and Standard Deviation) were reported. For timepoints below the LLOQ, only the Median and Max were reported as a separate outcome measure below.
Time frame: Pre-dose (0 hour) at Baseline and Weeks 14, 24, 44 and 66
Population: All participants who received at least one dose of study drug and had evaluable PK data. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 14 | 11.0 micrograms per millilitre (μg/mL) | Standard Deviation 4.66 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 14 | 12.7 micrograms per millilitre (μg/mL) | Standard Deviation 5.5 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 24 | 0.474 micrograms per millilitre (μg/mL) | Standard Deviation 0.742 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 14 | 14.0 micrograms per millilitre (μg/mL) | Standard Deviation 6.12 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 24 | 9.55 micrograms per millilitre (μg/mL) | Standard Deviation 5.24 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 44 | 10.7 micrograms per millilitre (μg/mL) | Standard Deviation 5.72 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) | Week 66 | 16.2 micrograms per millilitre (μg/mL) | Standard Deviation 7.75 |
Secondary
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)
As per Protocol, the timepoints for each arm where more than a third of the samples were below the LLOQ only the Median and Max were reported.
Time frame: Weeks 44 and 66
Population: All participants who received at least one dose of study drug and had evaluable PK data and were part of the timepoints that had more than a third of samples below LLOQ. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ) | Week 44 | 0.0400 micrograms per millilitre (μg/mL) |
| Cohort 2: Placebo (Double-Blind Induction Phase) | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ) | Week 66 | 0.0400 micrograms per millilitre (μg/mL) |
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)
The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.
Time frame: Baseline and Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Scores on a Scale | Standard Error 4.12 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | 37.4 Scores on a Scale | Standard Error 2.17 |
p-value: 0.044595% CI: [0.2, 17.9]ANCOVA
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
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.
Time frame: Baseline and Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Score on a Scale | Standard Error 0.6 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | -5.2 Score on a Scale | Standard Error 0.3 |
p-value: 0.269895% CI: [-2.9, -0.3]Mixed Models Analysis
Secondary
Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.
Time frame: Baseline and Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire | -1.1 Score on a Scale | Standard Error 0.2 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire | -1.5 Score on a Scale | Standard Error 0.1 |
p-value: 0.388195% CI: [-1, 0]Mixed Models Analysis
Secondary
Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore
Rectal bleeding data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = no blood in the stool; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed. The Mayo Clinic Score (MCS) rectal bleeding subscore was calculated as the worst value of three days of daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline rectal bleeding (RB) subscore.
Time frame: Baseline and Week 6
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore | -0.4 Score on a Scale | Standard Deviation 0.8 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore | -0.7 Score on a Scale | Standard Deviation 0.9 |
p-value: 0.035195% CI: [-0.5, 0]ANCOVA
Secondary
Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore
Stool frequency data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = normal number of stools; 1 = 1 to 2 more stools than normal; 2 = 3 to 4 more stools than normal; 3 = 5 or more stools than normal. The Mayo Clinic Score (MCS) stool frequency subscore was calculated as the average of three days daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline stool frequency (SF) subscore.
Time frame: Baseline and Week 6
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore | -0.5 Score on a Scale | Standard Deviation 0.9 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore | -0.6 Score on a Scale | Standard Deviation 1 |
p-value: 0.269895% CI: [-0.4, 0.1]ANCOVA
Secondary
Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time frame: Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS | 6.3 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS | 18.8 Percentage of Participants |
p-value: 0.002895% CI: [4.19, 17.94]Cochran-Mantel-Haenszel
Secondary
Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. 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 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS | 31.6 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS | 45.8 Percentage of Participants |
p-value: 0.024195% CI: [3.21, 24.14]Cochran-Mantel-Haenszel
Secondary
Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0.
Time frame: Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore | 9.5 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore | 17.2 Percentage of Participants |
p-value: 0.388195% CI: [-1.22, 13.66]Cochran-Mantel-Haenszel
Secondary
Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index
Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1.
Time frame: Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index | 25.0 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index | 29.7 Percentage of Participants |
p-value: 0.587995% CI: [-6.78, 14.69]Cochran-Mantel-Haenszel
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Time frame: Baseline and Week 14
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | 33.3 Percentage of Participants |
p-value: 0.160595% CI: [-2.54, 17.22]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ
The IBDQ is used to assess participant's health-related quality of life (QOL). The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.
Time frame: Baseline and Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Scores on a Scale | Standard Error 3.1 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ | 52.3 Scores on a Scale | Standard Error 3.1 |
p-value: 0.222895% CI: [-12.7, 3]ANCOVA
Secondary
Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.
Time frame: Baseline and Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Score on a Scale | Standard Error 0.6 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire | -7.8 Score on a Scale | Standard Error 0.6 |
p-value: 0.076395% CI: [-3.1, 0.2]Mixed Models Analysis
Secondary
Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.
Time frame: Baseline and Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire | -1.8 Score on a Scale | Standard Error 0.3 |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire | -2.0 Score on a Scale | Standard Error 0.3 |
p-value: 0.532995% CI: [-1, 0.5]Mixed Models Analysis
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | 38.1 Percentage of Participants |
p-value: 0.995995% CI: [-19.67, 19.88]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS | 21.1 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS | 25.0 Percentage of Participants |
p-value: 0.501495% CI: [-7.26, 14.7]Cochran-Mantel-Haenszel
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | 20.4 Percentage of Participants |
p-value: 0.301595% CI: [-6.83, 21.6]Cochran-Mantel-Haenszel
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | 18.5 Percentage of Participants |
p-value: 0.278795% CI: [-6.23, 21.17]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore | 11.4 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore | 23.2 Percentage of Participants |
p-value: 0.017495% CI: [1.87, 21.71]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index
Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index | 14.1 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index | 30.8 Percentage of Participants |
p-value: 0.007395% CI: [4.44, 28.41]Cochran-Mantel-Haenszel
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Time frame: Baseline and Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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 | 35.7 Percentage of Participants |
p-value: 0.015395% CI: [2.66, 25.78]Cochran-Mantel-Haenszel
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
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0.
Time frame: Week 66
Population: The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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 Percentage of Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS | 36.6 Percentage of Participants |
p-value: 0.953895% CI: [-19.08, 20.35]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time frame: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 2 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 1 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 12 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 4 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 9 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 10 Participants |
Secondary
Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study
A tiered strategy was used to detect and characterize etrolizumab antibodies within this clinical study. When determining post baseline incidence, participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following etrolizumab drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were ADA negative or had missing data at baseline and all post baseline samples were negative, or if they were ADA positive at baseline but did not have any post baseline samples with a titer that was at least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected).
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)
Population: Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result from at least one sample. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Baseline | 9 Participants |
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Post-Baseline | 68 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Baseline | 2 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Post-Baseline | 35 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Baseline | 6 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study | Post-Baseline | 28 Participants |
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)
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: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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) | Grade 4 | 0 Participants |
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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) | Grade 2 | 38 Participants |
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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) | Grade 1 | 39 Participants |
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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) | Grade 5 | 0 Participants |
| Cohort 2: Placebo (Double-Blind Induction Phase) | 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) | Grade 3 | 15 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 2 | 26 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 4 | 1 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 1 | 31 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 5 | 0 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 3 | 5 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 2 | 97 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 4 | 2 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 5 | 0 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 3 | 37 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | 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) | Grade 1 | 117 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | 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) | Grade 3 | 1 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | 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) | Grade 1 | 8 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | 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) | Grade 2 | 14 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | 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) | Grade 4 | 0 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | 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) | Grade 5 | 0 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | 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) | Grade 4 | 0 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | 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) | Grade 1 | 19 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | 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) | Grade 5 | 0 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | 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) | Grade 2 | 64 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | 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) | Grade 3 | 14 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | 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) | Grade 1 | 33 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | 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) | Grade 4 | 1 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | 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) | Grade 2 | 45 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | 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) | Grade 5 | 0 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | 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) | Grade 3 | 19 Participants |
Secondary
Number of Participants With Hypersensitivity Reaction-Related Adverse Events
Time frame: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Hypersensitivity Reaction-Related Adverse Events | 0 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Hypersensitivity Reaction-Related Adverse Events | 0 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Hypersensitivity Reaction-Related Adverse Events | 0 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | Number of Participants With Hypersensitivity Reaction-Related Adverse Events | 0 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | Number of Participants With Hypersensitivity Reaction-Related Adverse Events | 0 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Number of Participants With Hypersensitivity Reaction-Related Adverse Events | 0 Participants |
Secondary
Number of Participants With Infection-Related Adverse Events
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. 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: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Infection-Related Adverse Events | 38 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Infection-Related Adverse Events | 29 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Infection-Related Adverse Events | 100 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | Number of Participants With Infection-Related Adverse Events | 13 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | Number of Participants With Infection-Related Adverse Events | 44 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Number of Participants With Infection-Related Adverse Events | 58 Participants |
Secondary
Number of Participants With Injection-Site Reaction-Related Adverse Events
Time frame: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Injection-Site Reaction-Related Adverse Events | 7 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Injection-Site Reaction-Related Adverse Events | 5 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Injection-Site Reaction-Related Adverse Events | 4 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | Number of Participants With Injection-Site Reaction-Related Adverse Events | 2 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | Number of Participants With Injection-Site Reaction-Related Adverse Events | 2 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Number of Participants With Injection-Site Reaction-Related Adverse Events | 8 Participants |
Secondary
Number of Participants With Malignancies
Time frame: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Malignancies | 0 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Malignancies | 0 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Malignancies | 2 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | Number of Participants With Malignancies | 0 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | Number of Participants With Malignancies | 0 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Number of Participants With Malignancies | 2 Participants |
Secondary
Number of Participants With Serious Infection-Related Adverse Events
Time frame: From Baseline up to Week 78
Population: The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Placebo (Double-Blind Induction Phase) | Number of Participants With Serious Infection-Related Adverse Events | 2 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Serious Infection-Related Adverse Events | 1 Participants |
| Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Number of Participants With Serious Infection-Related Adverse Events | 5 Participants |
| Placebo Responders: Placebo (Maintenance Phase) | Number of Participants With Serious Infection-Related Adverse Events | 0 Participants |
| Etrolizumab Responders: Placebo (Maintenance Phase) | Number of Participants With Serious Infection-Related Adverse Events | 3 Participants |
| Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Number of Participants With Serious Infection-Related Adverse Events | 3 Participants |