Trial Outcomes & Findings for 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 (NCT NCT02100696)
NCT ID: NCT02100696
Last Updated: 2021-08-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
609 participants
Primary outcome timeframe
Week 14
Results posted on
2021-08-13
Participant Flow
The study was conducted at 184 centers in 24 countries.
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.
Participant milestones
| Measure |
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase.
|
Cohort 2: Placebo (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase
STARTED
|
130
|
95
|
384
|
0
|
0
|
0
|
|
Induction Phase
COMPLETED
|
115
|
90
|
358
|
0
|
0
|
0
|
|
Induction Phase
NOT COMPLETED
|
15
|
5
|
26
|
0
|
0
|
0
|
|
Maintenance Phase
STARTED
|
0
|
0
|
0
|
27
|
115
|
117
|
|
Maintenance Phase
COMPLETED
|
0
|
0
|
0
|
26
|
106
|
112
|
|
Maintenance Phase
NOT COMPLETED
|
0
|
0
|
0
|
1
|
9
|
5
|
Reasons for withdrawal
| Measure |
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase.
|
Cohort 2: Placebo (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Induction Phase
Lost to Follow-up
|
1
|
0
|
1
|
0
|
0
|
0
|
|
Induction Phase
Protocol Violation
|
0
|
1
|
1
|
0
|
0
|
0
|
|
Induction Phase
Withdrawal by Subject
|
8
|
2
|
13
|
0
|
0
|
0
|
|
Induction Phase
Physician Decision
|
1
|
0
|
2
|
0
|
0
|
0
|
|
Induction Phase
Multiple Reasons
|
5
|
2
|
8
|
0
|
0
|
0
|
|
Maintenance Phase
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Maintenance Phase
Lost to Follow-up
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Maintenance Phase
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Maintenance Phase
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
4
|
2
|
|
Maintenance Phase
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Maintenance Phase
Multiple Reasons
|
0
|
0
|
0
|
0
|
2
|
1
|
Baseline Characteristics
Participants in the Induction Phase of this study.
Baseline characteristics by cohort
| Measure |
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
n=130 Participants
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: Placebo (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=115 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=117 Participants
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
n=868 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
39.5 years
STANDARD_DEVIATION 13.5 • n=130 Participants • Participants in the Induction Phase of this study.
|
38.8 years
STANDARD_DEVIATION 13.9 • n=95 Participants • Participants in the Induction Phase of this study.
|
40.7 years
STANDARD_DEVIATION 13.3 • n=384 Participants • Participants in the Induction Phase of this study.
|
43.1 years
STANDARD_DEVIATION 13.8 • n=27 Participants • Participants in the Maintenance Phase of this study.
|
42.0 years
STANDARD_DEVIATION 13.5 • n=115 Participants • Participants in the Maintenance Phase of this study.
|
40.0 years
STANDARD_DEVIATION 12.9 • n=117 Participants • Participants in the Maintenance Phase of this study.
|
41.2 years
STANDARD_DEVIATION 13.2 • n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Sex: Female, Male
Female
|
52 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
41 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
160 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
9 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
43 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
57 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
109 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Sex: Female, Male
Male
|
78 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
54 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
224 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
18 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
72 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
60 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
150 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
4 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
5 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
30 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
1 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
8 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
9 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
18 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
118 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
76 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
321 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
21 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
95 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
94 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
210 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
Not Reported or Unknown
|
8 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
14 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
33 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
5 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
12 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
14 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
31 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
1 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
0 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
—
|
—
|
—
|
1 Participants
n=609 Participants • Participants in the Induction Phase of this study.
|
|
Race/Ethnicity, Customized
Asian
|
6 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
5 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
26 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
2 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
5 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
5 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
12 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
1 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
6 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
0 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
1 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
3 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
4 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
White
|
109 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
73 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
304 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
20 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
96 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
92 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
208 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
|
Race/Ethnicity, Customized
Other
|
12 Participants
n=130 Participants • Participants in the Induction Phase of this study.
|
15 Participants
n=95 Participants • Participants in the Induction Phase of this study.
|
48 Participants
n=384 Participants • Participants in the Induction Phase of this study.
|
5 Participants
n=27 Participants • Participants in the Maintenance Phase of this study.
|
13 Participants
n=115 Participants • Participants in the Maintenance Phase of this study.
|
17 Participants
n=117 Participants • Participants in the Maintenance Phase of this study.
|
35 Participants
n=259 Participants • Participants in the Maintenance Phase of this study.
|
PRIMARY outcome
Timeframe: Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS)
|
6.3 Percentage of Participants
|
18.5 Percentage of Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=114 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=112 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved a Clinical Response at Week 14, as Determined by the MCS
|
20.2 Percentage of Participants
|
24.1 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS
|
6.3 Percentage of Participants
|
18.8 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS
|
31.6 Percentage of Participants
|
45.8 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 14, as Determined by the MCS Endoscopic Subscore
|
25.3 Percentage of Participants
|
33.3 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore
|
9.5 Percentage of Participants
|
17.2 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=80 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=310 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index
|
25.0 Percentage of Participants
|
29.7 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=94 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=383 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore
|
-0.4 Score on a Scale
Standard Deviation 0.8
|
-0.7 Score on a Scale
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=94 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=383 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore
|
-0.5 Score on a Scale
Standard Deviation 0.9
|
-0.6 Score on a Scale
Standard Deviation 1.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=80 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=272 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Change From Baseline to Week 14 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire
|
-3.6 Score on a Scale
Standard Error 0.6
|
-5.2 Score on a Scale
Standard Error 0.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=80 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=272 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
|
-1.1 Score on a Scale
Standard Error 0.2
|
-1.5 Score on a Scale
Standard Error 0.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 14Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=74 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=293 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Induction Phase: Change From Baseline to Week 14 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ)
|
28.4 Scores on a Scale
Standard Error 4.12
|
37.4 Scores on a Scale
Standard Error 2.17
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=44 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=42 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 Among Participants Who Had Achieved Clinical Remission at Week 14, as Determined by the MCS
|
36.4 Percentage of Participants
|
38.1 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=114 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=112 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS
|
21.1 Percentage of Participants
|
25.0 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=44 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=41 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS
|
34.1 Percentage of Participants
|
36.6 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=114 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=112 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 66, as Determined by the MCS Endoscopic Subscore
|
21.1 Percentage of Participants
|
35.7 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=92 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=91 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index
|
14.1 Percentage of Participants
|
30.8 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=114 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=112 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore
|
11.4 Percentage of Participants
|
23.2 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=55 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=54 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS
|
12.7 Percentage of Participants
|
20.4 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=55 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=54 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS
|
10.9 Percentage of Participants
|
18.5 Percentage of Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=83 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=83 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire
|
-6.3 Score on a Scale
Standard Error 0.6
|
-7.8 Score on a Scale
Standard Error 0.6
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=83 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=83 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
|
-1.8 Score on a Scale
Standard Error 0.3
|
-2.0 Score on a Scale
Standard Error 0.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=99 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=99 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ
|
57.2 Scores on a Scale
Standard Error 3.1
|
52.3 Scores on a Scale
Standard Error 3.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Grade 1
|
39 Participants
|
31 Participants
|
117 Participants
|
8 Participants
|
19 Participants
|
33 Participants
|
|
Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Grade 2
|
38 Participants
|
26 Participants
|
97 Participants
|
14 Participants
|
64 Participants
|
45 Participants
|
|
Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Grade 4
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Grade 5
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Grade 3
|
15 Participants
|
5 Participants
|
37 Participants
|
1 Participants
|
14 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
|
2 Participants
|
1 Participants
|
12 Participants
|
4 Participants
|
9 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Serious Infection-Related Adverse Events
|
2 Participants
|
1 Participants
|
5 Participants
|
0 Participants
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Infection-Related Adverse Events
|
38 Participants
|
29 Participants
|
100 Participants
|
13 Participants
|
44 Participants
|
58 Participants
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Injection-Site Reaction-Related Adverse Events
|
7 Participants
|
5 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Hypersensitivity Reaction-Related Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline up to Week 78Population: 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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=130 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=95 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 Participants
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 Participants
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Malignancies
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Pre-dose at Baseline, Weeks 4, 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78)Population: Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result from at least one sample. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase.
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).
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=286 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=114 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=112 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study
Post-Baseline
|
68 Participants
|
35 Participants
|
28 Participants
|
—
|
—
|
—
|
|
Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study
Baseline
|
9 Participants
|
2 Participants
|
6 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour) at Baseline and Weeks 14, 24, 44 and 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=251 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=113 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=110 Participants
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
Week 14
|
11.0 micrograms per millilitre (μg/mL)
Standard Deviation 4.66
|
12.7 micrograms per millilitre (μg/mL)
Standard Deviation 5.50
|
14.0 micrograms per millilitre (μg/mL)
Standard Deviation 6.12
|
—
|
—
|
—
|
|
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
Week 24
|
—
|
0.474 micrograms per millilitre (μg/mL)
Standard Deviation 0.742
|
9.55 micrograms per millilitre (μg/mL)
Standard Deviation 5.24
|
—
|
—
|
—
|
|
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
Week 44
|
—
|
—
|
10.7 micrograms per millilitre (μg/mL)
Standard Deviation 5.72
|
—
|
—
|
—
|
|
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
Week 66
|
—
|
—
|
16.2 micrograms per millilitre (μg/mL)
Standard Deviation 7.75
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 44 and 66Population: 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.
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.
Outcome measures
| Measure |
Cohort 2: Placebo (Double-Blind Induction Phase)
n=113 Participants
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.
|
|---|---|---|---|---|---|---|
|
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)
Week 44
|
0.0400 micrograms per millilitre (μg/mL)
Interval to 2.73
As per Protocol, only the Median and Max were reported for timepoints where more than a third of the samples were below the LLOQ.
|
—
|
—
|
—
|
—
|
—
|
|
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)
Week 66
|
0.0400 micrograms per millilitre (μg/mL)
Interval to 0.04
As per Protocol, only the Median and Max were reported for timepoints where more than a third of the samples were below the LLOQ.
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
Serious events: 11 serious events
Other events: 38 other events
Deaths: 0 deaths
Cohort 2: Placebo (Double-Blind Induction Phase)
Serious events: 5 serious events
Other events: 31 other events
Deaths: 0 deaths
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Serious events: 20 serious events
Other events: 115 other events
Deaths: 0 deaths
Placebo Responders: Placebo (Maintenance Phase)
Serious events: 2 serious events
Other events: 20 other events
Deaths: 0 deaths
Etrolizumab Responders: Placebo (Maintenance Phase)
Serious events: 7 serious events
Other events: 78 other events
Deaths: 0 deaths
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Serious events: 11 serious events
Other events: 78 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
n=130 participants at risk
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: Placebo (Double-Blind Induction Phase)
n=95 participants at risk
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 participants at risk
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 participants at risk
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 participants at risk
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
2.1%
2/95 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/114 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
4.6%
6/130 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
2.1%
2/95 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
2.6%
10/384 • Number of events 10 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/114 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
1.1%
1/95 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Gastrointestinal necrosis
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Pouchitis
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
1.1%
1/95 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
General disorders
Oedema peripheral
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Abdominal abscess
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
1.1%
1/95 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Abscess
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/112 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Atypical pneumonia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Herpes zoster
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Influenza
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Osteomyelitis
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Viral infection
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleomorphic adenoma
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uteric cancer
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Nervous system disorders
Hypoaesthesia
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Nervous system disorders
Lethargy
|
0.77%
1/130 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Nervous system disorders
Myoclonus
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Psychiatric disorders
Affect liability
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Eosinophilic pneumonia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
|
Vascular disorders
Hypertension
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.26%
1/384 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.89%
1/112 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
Other adverse events
| Measure |
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
n=130 participants at risk
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: Placebo (Double-Blind Induction Phase)
n=95 participants at risk
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
|
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
n=384 participants at risk
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
|
Placebo Responders: Placebo (Maintenance Phase)
n=27 participants at risk
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.
|
Etrolizumab Responders: Placebo (Maintenance Phase)
n=114 participants at risk
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.
|
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
n=112 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
6.1%
7/114 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
8.9%
10/112 • Number of events 11 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
6.9%
9/130 • Number of events 9 • Baseline up until a maximum of 78 weeks.
|
10.5%
10/95 • Number of events 10 • Baseline up until a maximum of 78 weeks.
|
9.4%
36/384 • Number of events 37 • Baseline up until a maximum of 78 weeks.
|
40.7%
11/27 • Number of events 11 • Baseline up until a maximum of 78 weeks.
|
40.4%
46/114 • Number of events 52 • Baseline up until a maximum of 78 weeks.
|
27.7%
31/112 • Number of events 32 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
4.4%
5/114 • Number of events 5 • Baseline up until a maximum of 78 weeks.
|
5.4%
6/112 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
7.4%
2/27 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
3.5%
4/114 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
6.2%
7/112 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
|
General disorders
Asthenia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
7.4%
2/27 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
2.6%
3/114 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
4.5%
5/112 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
|
General disorders
Fatigue
|
6.2%
8/130 • Number of events 11 • Baseline up until a maximum of 78 weeks.
|
1.1%
1/95 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
2.6%
10/384 • Number of events 13 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
3.5%
4/114 • Number of events 4 • Baseline up until a maximum of 78 weeks.
|
10.7%
12/112 • Number of events 13 • Baseline up until a maximum of 78 weeks.
|
|
General disorders
Injection site erythema
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
7.4%
2/27 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/114 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
4.5%
5/112 • Number of events 9 • Baseline up until a maximum of 78 weeks.
|
|
General disorders
Pyrexia
|
3.8%
5/130 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
6.3%
6/95 • Number of events 8 • Baseline up until a maximum of 78 weeks.
|
0.78%
3/384 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/114 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/112 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
5.4%
6/112 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Influenza
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
7.9%
9/114 • Number of events 9 • Baseline up until a maximum of 78 weeks.
|
4.5%
5/112 • Number of events 5 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Nasopharyngitis
|
9.2%
12/130 • Number of events 12 • Baseline up until a maximum of 78 weeks.
|
7.4%
7/95 • Number of events 8 • Baseline up until a maximum of 78 weeks.
|
8.6%
33/384 • Number of events 35 • Baseline up until a maximum of 78 weeks.
|
14.8%
4/27 • Number of events 5 • Baseline up until a maximum of 78 weeks.
|
14.9%
17/114 • Number of events 22 • Baseline up until a maximum of 78 weeks.
|
20.5%
23/112 • Number of events 33 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
7.4%
2/27 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
4.5%
5/112 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
14.8%
4/27 • Number of events 5 • Baseline up until a maximum of 78 weeks.
|
4.4%
5/114 • Number of events 8 • Baseline up until a maximum of 78 weeks.
|
4.5%
5/112 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.8%
5/130 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
7.4%
7/95 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
8.6%
33/384 • Number of events 38 • Baseline up until a maximum of 78 weeks.
|
14.8%
4/27 • Number of events 6 • Baseline up until a maximum of 78 weeks.
|
7.0%
8/114 • Number of events 11 • Baseline up until a maximum of 78 weeks.
|
17.0%
19/112 • Number of events 26 • Baseline up until a maximum of 78 weeks.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
7.4%
2/27 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
0.88%
1/114 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/112 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
|
Nervous system disorders
Headache
|
7.7%
10/130 • Number of events 11 • Baseline up until a maximum of 78 weeks.
|
6.3%
6/95 • Number of events 8 • Baseline up until a maximum of 78 weeks.
|
5.7%
22/384 • Number of events 26 • Baseline up until a maximum of 78 weeks.
|
11.1%
3/27 • Number of events 3 • Baseline up until a maximum of 78 weeks.
|
8.8%
10/114 • Number of events 12 • Baseline up until a maximum of 78 weeks.
|
8.9%
10/112 • Number of events 10 • Baseline up until a maximum of 78 weeks.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/114 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
5.4%
6/112 • Number of events 8 • Baseline up until a maximum of 78 weeks.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/27 • Baseline up until a maximum of 78 weeks.
|
5.3%
6/114 • Number of events 7 • Baseline up until a maximum of 78 weeks.
|
3.6%
4/112 • Number of events 4 • Baseline up until a maximum of 78 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/130 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/95 • Baseline up until a maximum of 78 weeks.
|
0.00%
0/384 • Baseline up until a maximum of 78 weeks.
|
3.7%
1/27 • Number of events 1 • Baseline up until a maximum of 78 weeks.
|
1.8%
2/114 • Number of events 2 • Baseline up until a maximum of 78 weeks.
|
7.1%
8/112 • Number of events 12 • Baseline up until a maximum of 78 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER