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A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors (HICKORY)

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ClinicalTrials.gov Identifier: NCT02100696
Recruitment Status : Completed
First Posted : April 1, 2014
Results First Posted : June 15, 2021
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Ulcerative Colitis
Interventions Drug: Etrozulimab
Drug: Placebo
Enrollment 609
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.
Arm/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description 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. Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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. 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. 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. 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.
Period Title: Induction Phase
Started 130 95 384 0 0 0
Completed 115 90 358 0 0 0
Not Completed 15 5 26 0 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0             0
Lost to Follow-up             1             0             1             0             0             0
Protocol Violation             0             1             1             0             0             0
Withdrawal by Subject             8             2             13             0             0             0
Physician Decision             1             0             2             0             0             0
Multiple Reasons             5             2             8             0             0             0
Period Title: Maintenance Phase
Started 0 0 0 27 115 117
Completed 0 0 0 26 106 112
Not Completed 0 0 0 1 9 5
Reason Not Completed
Adverse Event             0             0             0             0             0             2
Lost to Follow-up             0             0             0             0             1             0
Protocol Violation             0             0             0             0             1             0
Withdrawal by Subject             0             0             0             1             4             2
Physician Decision             0             0             0             0             1             0
Multiple Reasons             0             0             0             0             2             1
Arm/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase) Total
Hide Arm/Group Description 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. Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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. 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 130 95 384 27 115 117 868
Hide Baseline Analysis Population Description
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.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
39.5  (13.5) 38.8  (13.9) 40.7  (13.3) 40.1  (13.4)
[1]
Measure Description: Induction Phase
[2]
Measure Analysis Population Description: Participants in the Induction Phase of this study.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
43.1  (13.8) 42.0  (13.5) 40.0  (12.9) 41.2  (13.2)
[1]
Measure Description: Maintenance Phase
[2]
Measure Analysis Population Description: Participants in the Maintenance Phase of this study.
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
Female
52
  40.0%
41
  43.2%
160
  41.7%
253
  41.5%
Male
78
  60.0%
54
  56.8%
224
  58.3%
356
  58.5%
[1]
Measure Description: Induction Phase
[2]
Measure Analysis Population Description: Participants in the Induction Phase of this study.
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
Female
9
  33.3%
43
  37.4%
57
  48.7%
109
  42.1%
Male
18
  66.7%
72
  62.6%
60
  51.3%
150
  57.9%
[1]
Measure Description: Maintenance Phase
[2]
Measure Analysis Population Description: Participants in the Maintenance Phase of this study.
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
4 5 30 39
Not Hispanic or Latino Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
118 76 321 515
Not Reported or Unknown Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
8 14 33 55
American Indian or Alaska Native Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
0 1 0 1
Asian Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
6 5 26 37
Black or African American Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
3 1 6 10
White Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
109 73 304 486
Other Number Analyzed 130 participants 95 participants 384 participants 0 participants 0 participants 0 participants 609 participants
12 15 48 75
[1]
Measure Description: Induction Phase
[2]
Measure Analysis Population Description: Participants in the Induction Phase of this study.
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
1 8 9 18
Not Hispanic or Latino Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
21 95 94 210
Not Reported or Unknown Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
5 12 14 31
Asian Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
2 5 5 12
Black or African American Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
0 1 3 4
White Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
20 96 92 208
Other Number Analyzed 0 participants 0 participants 0 participants 27 participants 115 participants 117 participants 259 participants
5 13 17 35
[1]
Measure Description: Maintenance Phase
[2]
Measure Analysis Population Description: Participants in the Maintenance Phase of this study.
1.Primary Outcome
Title Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 95 384
Measure Type: Number
Unit of Measure: Percentage of Participants
6.3 18.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0033
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted difference in response rates
Estimated Value 12.2
Confidence Interval (2-Sided) 95%
3.95 to 17.67
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 114 112
Measure Type: Number
Unit of Measure: Percentage of Participants
20.2 24.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4956
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-7.13 to 14.56
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 95 384
Measure Type: Number
Unit of Measure: Percentage of Participants
6.3 18.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 12.5
Confidence Interval (2-Sided) 95%
4.19 to 17.94
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 95 384
Measure Type: Number
Unit of Measure: Percentage of Participants
31.6 45.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0121
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Response Rates
Estimated Value 14.3
Confidence Interval (2-Sided) 95%
3.21 to 24.14
Estimation Comments [Not Specified]
5.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 95 384
Measure Type: Number
Unit of Measure: Percentage of Participants
25.3 33.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1204
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Response Rates
Estimated Value 8.1
Confidence Interval (2-Sided) 95%
-2.54 to 17.22
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 95 384
Measure Type: Number
Unit of Measure: Percentage of Participants
9.5 17.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0647
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
-1.22 to 13.66
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 80 310
Measure Type: Number
Unit of Measure: Percentage of Participants
25.0 29.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3920
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 4.9
Confidence Interval (2-Sided) 95%
-6.78 to 14.69
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 94 383
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
-0.4  (0.8) -0.7  (0.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Unadjusted Means
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to -0.0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 94 383
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
-0.5  (0.9) -0.6  (1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1124
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Unadjusted Means
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.1
Estimation Comments [Not Specified]
10.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 80 272
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-3.6  (0.6) -5.2  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0163
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-2.9 to -0.3
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 80 272
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-1.1  (0.2) -1.5  (0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0726
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.0 to 0.0
Estimation Comments [Not Specified]
12.Secondary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Hide Arm/Group Description:
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
Overall Number of Participants Analyzed 74 293
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a Scale
28.4  (4.12) 37.4  (2.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0445
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 9.1
Confidence Interval (2-Sided) 95%
0.2 to 17.9
Estimation Comments [Not Specified]
13.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 44 42
Measure Type: Number
Unit of Measure: Percentage of Participants
36.4 38.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9959
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-19.67 to 19.88
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 114 112
Measure Type: Number
Unit of Measure: Percentage of Participants
21.1 25.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5014
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-7.26 to 14.70
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: Percentage of Participants
34.1 36.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9538
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-19.08 to 20.35
Estimation Comments [Not Specified]
16.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 114 112
Measure Type: Number
Unit of Measure: Percentage of Participants
21.1 35.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0153
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Response Rates
Estimated Value 14.5
Confidence Interval (2-Sided) 95%
2.66 to 25.78
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 92 91
Measure Type: Number
Unit of Measure: Percentage of Participants
14.1 30.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0073
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 16.8
Confidence Interval (2-Sided) 95%
4.44 to 28.41
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 114 112
Measure Type: Number
Unit of Measure: Percentage of Participants
11.4 23.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0174
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 11.9
Confidence Interval (2-Sided) 95%
1.87 to 21.71
Estimation Comments [Not Specified]
19.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 55 54
Measure Type: Number
Unit of Measure: Percentage of Participants
12.7 20.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3015
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
-6.83 to 21.60
Estimation Comments [Not Specified]
20.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 55 54
Measure Type: Number
Unit of Measure: Percentage of Participants
10.9 18.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2787
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference in Remission Rates
Estimated Value 7.4
Confidence Interval (2-Sided) 95%
-6.23 to 21.17
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 83 83
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-6.3  (0.6) -7.8  (0.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0763
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.1 to 0.2
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 83 83
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-1.8  (0.3) -2.0  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5329
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.0 to 0.5
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 99 99
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a Scale
57.2  (3.1) 52.3  (3.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etrolizumab Responders: Placebo (Maintenance Phase), Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2228
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-12.7 to 3.0
Estimation Comments [Not Specified]
24.Secondary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
Grade 1 39 31 117 8 19 33
Grade 2 38 26 97 14 64 45
Grade 3 15 5 37 1 14 19
Grade 4 0 1 2 0 0 1
Grade 5 0 0 0 0 0 0
25.Secondary Outcome
Title Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Hide Description [Not Specified]
Time Frame From Baseline up to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
2 1 12 4 9 10
26.Secondary Outcome
Title Number of Participants With Serious Infection-Related Adverse Events
Hide Description [Not Specified]
Time Frame From Baseline up to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
2 1 5 0 3 3
27.Secondary Outcome
Title Number of Participants With Infection-Related Adverse Events
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
38 29 100 13 44 58
28.Secondary Outcome
Title Number of Participants With Injection-Site Reaction-Related Adverse Events
Hide Description [Not Specified]
Time Frame From Baseline up to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
7 5 4 2 2 8
29.Secondary Outcome
Title Number of Participants With Hypersensitivity Reaction-Related Adverse Events
Hide Description [Not Specified]
Time Frame From Baseline up to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
0 0 0 0 0 0
30.Secondary Outcome
Title Number of Participants With Malignancies
Hide Description [Not Specified]
Time Frame From Baseline up to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:
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.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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.
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.
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.
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.
Overall Number of Participants Analyzed 130 95 384 27 114 112
Measure Type: Number
Unit of Measure: Participants
0 0 2 0 0 2
31.Secondary Outcome
Title Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (OLI Phase) + Cohort 2: Etrolizumab (Double-Blind Induction Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:

Cohort 1: 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.

Cohort 2: Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. Participants in this arm did not enter into the Maintenance phase of the study.

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.
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.
Overall Number of Participants Analyzed 286 114 112
Measure Type: Number
Unit of Measure: Participants
Baseline Number Analyzed 286 participants 114 participants 110 participants
9 2 6
Post-Baseline Number Analyzed 284 participants 114 participants 112 participants
68 35 28
32.Secondary Outcome
Title Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: Etrolizumab (OLI Phase) + Cohort 2: Etrolizumab (Double-Blind Induction Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description:

Cohort 1: 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.

Cohort 2: Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. Participants in this arm did not enter into the Maintenance phase of the study.

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.
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.
Overall Number of Participants Analyzed 251 113 110
Mean (Standard Deviation)
Unit of Measure: micrograms per millilitre (μg/mL)
Week 14 Number Analyzed 251 participants 113 participants 110 participants
11.0  (4.66) 12.7  (5.50) 14.0  (6.12)
Week 24 Number Analyzed 0 participants 93 participants 92 participants
0.474  (0.742) 9.55  (5.24)
Week 44 Number Analyzed 0 participants 0 participants 71 participants
10.7  (5.72)
Week 66 Number Analyzed 0 participants 0 participants 59 participants
16.2  (7.75)
33.Secondary Outcome
Title Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Etrolizumab Responders: Placebo (Maintenance Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 113
Median (Full Range)
Unit of Measure: micrograms per millilitre (μg/mL)
Week 44 Number Analyzed 54 participants
0.0400 [1] 
(NA to 2.73)
Week 66 Number Analyzed 40 participants
0.0400 [1] 
(NA to 0.0400)
[1]
As per Protocol, only the Median and Max were reported for timepoints where more than a third of the samples were below the LLOQ.
Time Frame Baseline up until a maximum of 78 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Hide Arm/Group Description 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. Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the 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. 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. 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. 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.
All-Cause Mortality
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/130 (0.00%)      0/95 (0.00%)      0/384 (0.00%)      0/27 (0.00%)      0/114 (0.00%)      0/112 (0.00%)    
Hide Serious Adverse Events
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/130 (8.46%)      5/95 (5.26%)      20/384 (5.21%)      2/27 (7.41%)      7/114 (6.14%)      11/112 (9.82%)    
Blood and lymphatic system disorders             
Anaemia  1  0/130 (0.00%)  0 2/95 (2.11%)  3 1/384 (0.26%)  1 0/27 (0.00%)  0 2/114 (1.75%)  2 0/112 (0.00%)  0
Gastrointestinal disorders             
Cheilitis  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Colitis ulcerative  1  6/130 (4.62%)  6 2/95 (2.11%)  3 10/384 (2.60%)  10 0/27 (0.00%)  0 2/114 (1.75%)  2 1/112 (0.89%)  1
Diarrhoea  1  0/130 (0.00%)  0 1/95 (1.05%)  1 1/384 (0.26%)  1 1/27 (3.70%)  1 0/114 (0.00%)  0 0/112 (0.00%)  0
Gastrointestinal necrosis  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Intestinal haemorrhage  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Pouchitis  1  0/130 (0.00%)  0 1/95 (1.05%)  1 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
General disorders             
Oedema peripheral  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 1/114 (0.88%)  1 0/112 (0.00%)  0
Infections and infestations             
Abdominal abscess  1  0/130 (0.00%)  0 1/95 (1.05%)  1 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Abscess  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Appendicitis  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 2/112 (1.79%)  2
Atypical pneumonia  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 1/114 (0.88%)  1 0/112 (0.00%)  0
Clostridium difficile infection  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 1/114 (0.88%)  1 0/112 (0.00%)  0
Cytomegalovirus infection  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 1/114 (0.88%)  1 0/112 (0.00%)  0
Erysipelas  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Herpes zoster  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Influenza  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Osteomyelitis  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Pneumonia bacterial  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 1/114 (0.88%)  1 0/112 (0.00%)  0
Tonsillitis  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Upper respiratory tract infection  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Viral infection  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Metabolism and nutrition disorders             
Hypokalaemia  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Musculoskeletal and connective tissue disorders             
Back pain  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Myalgia  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Basal cell carcinoma  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Pleomorphic adenoma  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Uteric cancer  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Nervous system disorders             
Hypoaesthesia  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Lethargy  1  1/130 (0.77%)  1 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Myoclonus  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Psychiatric disorders             
Affect liability  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Renal and urinary disorders             
Renal colic  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 1/27 (3.70%)  1 0/114 (0.00%)  0 0/112 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Asthma  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Eosinophilic pneumonia  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
Vascular disorders             
Hypertension  1  0/130 (0.00%)  0 0/95 (0.00%)  0 1/384 (0.26%)  1 0/27 (0.00%)  0 0/114 (0.00%)  0 1/112 (0.89%)  1
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Cohort 2: Placebo (Double-Blind Induction Phase) Cohort 2: Etrolizumab (Double-Blind Induction Phase) Placebo Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Placebo (Maintenance Phase) Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/130 (29.23%)      31/95 (32.63%)      115/384 (29.95%)      20/27 (74.07%)      78/114 (68.42%)      78/112 (69.64%)    
Gastrointestinal disorders             
Abdominal pain  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 1/27 (3.70%)  1 7/114 (6.14%)  7 10/112 (8.93%)  11
Colitis ulcerative  1  9/130 (6.92%)  9 10/95 (10.53%)  10 36/384 (9.38%)  37 11/27 (40.74%)  11 46/114 (40.35%)  52 31/112 (27.68%)  32
Diarrhoea  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 1/27 (3.70%)  1 5/114 (4.39%)  5 6/112 (5.36%)  6
Nausea  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 2/27 (7.41%)  2 4/114 (3.51%)  7 7/112 (6.25%)  7
General disorders             
Asthenia  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 2/27 (7.41%)  3 3/114 (2.63%)  3 5/112 (4.46%)  6
Fatigue  1  8/130 (6.15%)  11 1/95 (1.05%)  1 10/384 (2.60%)  13 1/27 (3.70%)  1 4/114 (3.51%)  4 12/112 (10.71%)  13
Injection site erythema  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 2/27 (7.41%)  2 2/114 (1.75%)  3 5/112 (4.46%)  9
Pyrexia  1  5/130 (3.85%)  7 6/95 (6.32%)  8 3/384 (0.78%)  3 0/27 (0.00%)  0 0/114 (0.00%)  0 0/112 (0.00%)  0
Infections and infestations             
Gastroenteritis viral  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 1/114 (0.88%)  1 6/112 (5.36%)  6
Influenza  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 1/27 (3.70%)  1 9/114 (7.89%)  9 5/112 (4.46%)  5
Nasopharyngitis  1  12/130 (9.23%)  12 7/95 (7.37%)  8 33/384 (8.59%)  35 4/27 (14.81%)  5 17/114 (14.91%)  22 23/112 (20.54%)  33
Oral herpes  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 2/27 (7.41%)  2 1/114 (0.88%)  1 5/112 (4.46%)  6
Upper respiratory tract infection  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 4/27 (14.81%)  5 5/114 (4.39%)  8 5/112 (4.46%)  7
Musculoskeletal and connective tissue disorders             
Arthralgia  1  5/130 (3.85%)  6 7/95 (7.37%)  7 33/384 (8.59%)  38 4/27 (14.81%)  6 8/114 (7.02%)  11 19/112 (16.96%)  26
Nervous system disorders             
Dizziness  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 2/27 (7.41%)  2 1/114 (0.88%)  1 2/112 (1.79%)  2
Headache  1  10/130 (7.69%)  11 6/95 (6.32%)  8 22/384 (5.73%)  26 3/27 (11.11%)  3 10/114 (8.77%)  12 10/112 (8.93%)  10
Psychiatric disorders             
Insomnia  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 2/114 (1.75%)  2 6/112 (5.36%)  8
Skin and subcutaneous tissue disorders             
Pruritus  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 0/27 (0.00%)  0 6/114 (5.26%)  7 4/112 (3.57%)  4
Rash  1  0/130 (0.00%)  0 0/95 (0.00%)  0 0/384 (0.00%)  0 1/27 (3.70%)  1 2/114 (1.75%)  2 8/112 (7.14%)  12
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02100696    
Other Study ID Numbers: GA28950
2013-004278-88 ( EudraCT Number )
First Submitted: March 27, 2014
First Posted: April 1, 2014
Results First Submitted: April 9, 2021
Results First Posted: June 15, 2021
Last Update Posted: June 15, 2021