Crohn Disease
Conditions
Brief summary
This is a multicenter, Phase 3, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of etrolizumab compared with placebo during induction and maintenance treatment of moderately to severely active Crohn's Disease (CD). The target population includes participants with CD who are refractory or intolerant to corticosteroids (CS) and/or immunosuppressant (IS) therapy and who have either not received prior anti-tumor necrosis factor (anti-TNF) therapy (TNF-naive) or who have had prior exposure to anti-TNF therapies and demonstrated inadequate responses or intolerance to anti-TNFs. The study period will consist of a Screening Phase (up to 35 days) plus (+) a 14-week Induction Phase + a 52-week Maintenance Phase + a 12-week Safety Follow-up Phase. At Week 14 (end of Induction Phase), participants achieving a decrease from baseline of at least 70 points in the Crohn's Disease Activity Index (CDAI) score (CDAI-70 response) without the use of rescue therapy will continue to the Maintenance Phase.
Interventions
DRUGEtrolizumab
Etrolizumab will be administered as per regimen specified in individual arms.
DRUGPlacebo
Etrolizumab-matching placebo will be administered as per regimen specified in individual arms.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Moderately to severely active Crohn's Disease (CD) as determined by the CDAI, patient reported outcomes and endoscopically defined disease activity in the ileum and/or colon * Intolerance, refractory disease, or no response to corticosteroids (CS), immunosuppressants (IS), or anti-TNF therapy within 5 years from screening. Participants who have not previously demonstrated inadequate response or intolerance to one or more anti-TNF therapies are eligible to participate in the study provided they are intolerant or refractory to CS or IS therapy * Use of effective contraception as defined by the protocol
Exclusion criteria
* A history of, or current conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome * Planned surgery for CD * Ileostomy or colostomy * Has received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, and efalizumab, as stated in the protocol) * Any prior treatment with ustekinumab within 14 weeks prior to randomization * Chronic hepatitis B or C infection, human immunodeficiency virus (HIV), active or latent tuberculosis (participants with prior history of Bacillus Calmette-Guérin \[BCG\] vaccination must pass protocol-defined screening criteria) * Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical judgment of the investigator. Fistulas related to CD are not exclusionary * Any prior treatment with anti-adhesion molecules (e.g., anti-mucosal addressin cell adhesion molecule \[anti-MAdCAM-1\]) * Any major episode of infection requiring treatment with intravenous antibiotics ≤8 weeks prior to screening or oral antibiotics ≤4 weeks prior to screening. Treatment with antibiotics as adjunctive therapy for CD in the absence of documented infection is not exclusionary * Hospitalization (other than for elective reasons) within 4 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14 | Week 14 | Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. |
| Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 | Week 14 | Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. |
| Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14 | Week 14 | Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score. |
| Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 | Week 14 | Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score. |
| Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 | Baseline and Week 66 | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Maintenance phase participants were evaluated. |
| Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 | Week 66 | Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Maintenance phase participants were evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, Among Those Who Achieved Clinical Remission at Week 14 | Baseline, Weeks 14 and 66 | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Induction Phase Cohorts are not included |
| Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline | Baseline and Week 66 | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Induction Phase Cohorts are not included |
| Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 Among Participants Who Achieved Endoscopic Improvement at Week 14 | Baseline, Weeks 14 and 66 | Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Induction Phase Cohorts are not included |
| Maintenance Phase: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score >1, at Week 66 | Week 66 | Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity. |
| Maintenance Phase: Percentage of Participants With Durable Clinical Remission | Week 14 up to Week 66 (assessed at Weeks 24, 28, 32, 44, 56, and 66) | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Durable clinical remission was defined as clinical remission at ≥4 of the 6 in-clinic assessment visits conducted during the Maintenance Phase at Weeks 24, 28, 32, 44, 56, and 66. Induction Phase Cohorts are not included |
| Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline | Baseline and from Week 14 up to Week 66 | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Percentage of participants with clinical remission who will be off corticosteroids for at least 24 weeks prior to Week 66 will be reported. Induction Phase Cohorts are not included |
| Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66 | Baseline and Week 66 | CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available. |
| Overall Number of Participants Who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | From Baseline up to Week 78 | Investigator text for AEs is coded using MedDRA version 24.0. For participants counts, multiple occurrences of AEs in the same category for an individual are counted only once. For event counts, multiple occurrences of AEs in the same category for an individual are counted separately. Severity Grades from 1 to 5. |
| Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6 | Week 6 | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. |
| Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | From Baseline up to Week 78 | Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 are reported. 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 indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = Death. The terms 'severe' and 'serious' are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs are counted only once per participant at the highest (worst) grade. Infections are identified by Primary System Organ Class term 'Infections and Infestations' |
| Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | From Baseline up to Week 78 | Investigator text for AEs is coded using MedDRA version 24.0. Infections are identified by primary System Organ Class term 'Infections and Infestations'. The terms 'severe' and 'serious' are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs in the same category for an individual are counted only once |
| Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | From Baseline up to Week 78 | Investigator test for AEs is coding using MedDRA version 24.0. Injection-Site Reactions are identified by eCRF checkbox for local injection site reactions, and/or primary or secondary HLT Injection Site Reactions. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported. |
| Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | From Baseline up to Week 78 | Investigator text for AEs is coded using MedDRA version 24.0. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported. |
| Overall Number of Participants Who Develop Malignancies | From Baseline up to Week 78 | Participants with malignancies are reported. 'Malignancies are identified by SMQ Malignant and unspecified tumors (narrow) |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline, Pre-dose (Hour 0) on Weeks 4, 14, 24, 32, 44, 66 or early termination, 12 weeks after last dose (up to Week 78) | Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result. Induction: treatment groups were pooled across cohorts 1-3. Maintenance: treatment group is stratified by induction dose |
| Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Induction Phase at Weeks 10 and 14, Maintenance Phase at Weeks 16, 24, 28, 32, 44, and 66 | Serum Etrolizumab Trough Concentration |
| Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | From Baseline up to Week 78 | Number of participants who discontinued the study due to the adverse events is reported. |
| Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 | Week 6 | Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. |
| Induction Phase: Cohort 1: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | Week 14 | Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity. |
| Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | Week 14 | Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity. |
| Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | Baseline and Week 14 | CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available. |
| Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | Baseline and Week 14 | CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czechia, Estonia, France, Germany, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
At the time of study closure, a total of 1035 patients were randomized into the induction phase, enrolled sequentially across Cohorts 1, 2, and 3. The final sample size for the pivotal induction Cohort 3 was lower than the 496 patients planned per the final protocol due to the early closure of the study. Cohorts below are mutually exclusive.
Pre-assignment details
A total of 1035 participants entered the study across induction cohorts 1-3, a subset of 487 patients moved into the maintenance phase of the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Cohort 1 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking. | 59 |
| Etrolizumab 105mg Cohort 1 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. | 120 |
| Etrolizumab 210mg Cohort 1 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. | 121 |
| Etrolizumab 105mg Cohort 2 Cohort 2 enrolled participants after Cohort 1 and was considered a feeder cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. | 176 |
| Etrolizumab 210mg Cohort 2 Cohort 2 enrolled participants after Cohort 1 and was considered a feeder cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. | 174 |
| Placebo Cohort 3 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking. | 96 |
| Etrolizumab 105mg Cohort 3 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. | 143 |
| Etrolizumab 210mg Cohort 3 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. | 145 |
| Maintenance Phase - Placebo Responders: Placebo Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 underwent a sham randomization into the Maintenance Phase. Placebo responders from induction received blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64. | 53 |
| Maintenance Phase - Etrolizumab Responders: Placebo Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm received blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64. | 217 |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm received blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64. | 217 |
| Total | 1,521 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction Phase | :ack of calculation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Induction Phase | Adverse Event | 2 | 4 | 1 | 2 | 5 | 2 | 0 | 0 | 0 | 0 | 0 |
| Induction Phase | Early withdrawal and roll over to a different study | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Induction Phase | Lack of Efficacy | 3 | 6 | 2 | 17 | 14 | 8 | 17 | 23 | 0 | 0 | 0 |
| Induction Phase | Lost to Follow-up | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Induction Phase | Non-compliance | 0 | 1 | 3 | 1 | 3 | 0 | 1 | 1 | 0 | 0 | 0 |
| Induction Phase | Physician Decision | 0 | 0 | 1 | 4 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Induction Phase | Protocol Violation | 0 | 2 | 0 | 3 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Induction Phase | Sponsor decision | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Phase | Technical reason | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Phase | Withdrawal by Subject | 1 | 2 | 4 | 6 | 7 | 4 | 3 | 6 | 0 | 0 | 0 |
| Maintenance Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 |
| Maintenance Phase | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Maintenance Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 25 | 33 |
| Maintenance Phase | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 2 |
| Maintenance Phase | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Maintenance Phase | Site closure | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 12 | 12 |
Baseline characteristics
| Characteristic | Placebo Cohort 3 | Placebo Cohort 1 | Etrolizumab 105mg Cohort 1 | Etrolizumab 210mg Cohort 1 | Etrolizumab 105mg Cohort 2 | Etrolizumab 210mg Cohort 2 | Etrolizumab 105mg Cohort 3 | Etrolizumab 210mg Cohort 3 | Total | Maintenance Phase - Placebo Responders: Placebo | Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Induction Phase | 37.1 Years STANDARD_DEVIATION 13.6 | 36.5 Years STANDARD_DEVIATION 12.7 | 38.9 Years STANDARD_DEVIATION 13.1 | 38.6 Years STANDARD_DEVIATION 13.4 | 38.4 Years STANDARD_DEVIATION 13.3 | 38.2 Years STANDARD_DEVIATION 13.2 | 38.3 Years STANDARD_DEVIATION 13.4 | 36.5 Years STANDARD_DEVIATION 13.1 | 37.9 Years STANDARD_DEVIATION 13.2 | — | — | — |
| Age, Continuous Maintenance Phase | — | — | — | — | — | — | — | — | 38.3 Years STANDARD_DEVIATION 12.8 | 38.2 Years STANDARD_DEVIATION 13.3 | 37.9 Years STANDARD_DEVIATION 12.6 | 38.8 Years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Induction Phase Hispanic or Latino | 15 Participants | 2 Participants | 5 Participants | 5 Participants | 7 Participants | 8 Participants | 13 Participants | 7 Participants | 62 Participants | — | — | — |
| Ethnicity (NIH/OMB) Induction Phase Not Hispanic or Latino | 74 Participants | 53 Participants | 110 Participants | 113 Participants | 160 Participants | 154 Participants | 126 Participants | 129 Participants | 919 Participants | — | — | — |
| Ethnicity (NIH/OMB) Induction Phase Unknown or Not Reported | 7 Participants | 4 Participants | 5 Participants | 3 Participants | 9 Participants | 12 Participants | 4 Participants | 9 Participants | 53 Participants | — | — | — |
| Ethnicity (NIH/OMB) Maintenance Phase Hispanic or Latino | — | — | — | — | — | — | — | — | 29 Participants | 7 Participants | 10 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Maintenance Phase Not Hispanic or Latino | — | — | — | — | — | — | — | — | 437 Participants | 41 Participants | 199 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Maintenance Phase Unknown or Not Reported | — | — | — | — | — | — | — | — | 21 Participants | 5 Participants | 8 Participants | 8 Participants |
| Race/Ethnicity, Customized Induction Phase American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants | — | — | — |
| Race/Ethnicity, Customized Induction Phase Asian | 0 Participants | 5 Participants | 9 Participants | 7 Participants | 8 Participants | 14 Participants | 4 Participants | 2 Participants | 49 Participants | — | — | — |
| Race/Ethnicity, Customized Induction Phase Black or African American | 6 Participants | 3 Participants | 5 Participants | 2 Participants | 1 Participants | 5 Participants | 8 Participants | 2 Participants | 32 Participants | — | — | — |
| Race/Ethnicity, Customized Induction Phase Multiple | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | — | — | — |
| Race/Ethnicity, Customized Induction Phase Other | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 5 Participants | 22 Participants | — | — | — |
| Race/Ethnicity, Customized Induction Phase Unknown | 6 Participants | 4 Participants | 7 Participants | 5 Participants | 10 Participants | 12 Participants | 8 Participants | 7 Participants | 59 Participants | — | — | — |
| Race/Ethnicity, Customized Induction Phase White | 80 Participants | 46 Participants | 96 Participants | 104 Participants | 153 Participants | 141 Participants | 117 Participants | 128 Participants | 865 Participants | — | — | — |
| Race/Ethnicity, Customized Maintenance Phase American Indian or Alaska Native | — | — | — | — | — | — | — | — | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Maintenance Phase Asian | — | — | — | — | — | — | — | — | 19 Participants | 0 Participants | 8 Participants | 11 Participants |
| Race/Ethnicity, Customized Maintenance Phase Black or African American | — | — | — | — | — | — | — | — | 16 Participants | 2 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Maintenance Phase Multiple | — | — | — | — | — | — | — | — | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Maintenance Phase Other | — | — | — | — | — | — | — | — | 13 Participants | 2 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Maintenance Phase Unknown | — | — | — | — | — | — | — | — | 16 Participants | 3 Participants | 6 Participants | 7 Participants |
| Race/Ethnicity, Customized Maintenance Phase White | — | — | — | — | — | — | — | — | 420 Participants | 45 Participants | 193 Participants | 182 Participants |
| Sex: Female, Male Induction Phase Female | 38 Participants | 31 Participants | 57 Participants | 68 Participants | 80 Participants | 80 Participants | 69 Participants | 69 Participants | 492 Participants | — | — | — |
| Sex: Female, Male Induction Phase Male | 58 Participants | 28 Participants | 63 Participants | 53 Participants | 96 Participants | 94 Participants | 74 Participants | 76 Participants | 542 Participants | — | — | — |
| Sex: Female, Male Maintenance Phase Female | — | — | — | — | — | — | — | — | 240 Participants | 24 Participants | 118 Participants | 98 Participants |
| Sex: Female, Male Maintenance Phase Male | — | — | — | — | — | — | — | — | 247 Participants | 29 Participants | 99 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 120 | 0 / 121 | 0 / 176 | 0 / 174 | 0 / 96 | 0 / 143 | 0 / 145 | 0 / 53 | 0 / 217 | 1 / 217 |
| other Total, other adverse events | 32 / 59 | 61 / 120 | 52 / 121 | 80 / 176 | 68 / 174 | 35 / 96 | 65 / 143 | 45 / 145 | 33 / 53 | 154 / 217 | 147 / 217 |
| serious Total, serious adverse events | 8 / 59 | 20 / 120 | 12 / 121 | 18 / 176 | 20 / 174 | 8 / 96 | 12 / 143 | 8 / 145 | 9 / 53 | 33 / 217 | 30 / 217 |
Outcome results
Primary
Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14
Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
Time frame: Week 14
Population: mITT - Modified Intent to Treat population: all patients randomized who received at least one dose of study drug, grouped under the randomized treatment arm. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14 | 11.9 Percentage of Particiapnts |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14 | 20.00 Percentage of Particiapnts |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14 | 27.3 Percentage of Particiapnts |
Primary
Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14
Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.
Time frame: Week 14
Population: mITT. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14 | 3.4 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14 | 19.5 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14 | 16.8 Percentage of Participants |
Primary
Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14
Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
Time frame: Week 14
Population: mITT - Modified Intent to Treat population: all patients randomized who received at least one dose of study drug, grouped under the randomized treatment arm. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 | 29.5 Percentage of Particiapnts |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 | 29.3 Percentage of Particiapnts |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 | 29.2 Percentage of Particiapnts |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 | 30.1 Percentage of Particiapnts |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 | 33.1 Percentage of Particiapnts |
p-value: 0.850895% CI: [-10.85, 12.56]Cochran-Mantel-Haenszel
p-value: 0.523595% CI: [-8.3, 15.27]Cochran-Mantel-Haenszel
Primary
Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14
Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.
Time frame: Week 14
Population: mITT. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 | 20.8 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 | 22.2 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 | 21.6 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 | 26.2 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 | 27.4 Percentage of Participants |
p-value: 0.790895% CI: [-6.26, 16.11]Cochran-Mantel-Haenszel
p-value: 0.31795% CI: [-5.43, 17.05]Cochran-Mantel-Haenszel
Primary
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Maintenance phase participants were evaluated.
Time frame: Baseline and Week 66
Population: mITT. Maintenance Phase Placebo/Placebo cohort is not reported since this is an exploratory population only. Results for the Induction phase populations for cohorts 1-3 are not presented
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 | 24.00 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 | 35.00 Percentage of Participants |
p-value: 0.008895% CI: [2.7, 19.65]Cochran-Mantel-Haenszel
Primary
Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66
Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Maintenance phase participants were evaluated.
Time frame: Week 66
Population: mITT. Maintenance Phase Placebo/Placebo cohort is not reported since this is an exploratory population only. Induction Phase population for cohorts 1-3 are not included
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 | 12.2 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 | 23.6 Percentage of Participants |
p-value: 0.002695% CI: [4.11, 18.83]Cochran-Mantel-Haenszel
Secondary
Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14
CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.
Time frame: Baseline and Week 14
Population: mITT. Data evaluable participants are included. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented. Only patients with a baseline score and at least one post-baseline score are included in the analysis
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -0.7 scores on a scale | Standard Error 0.4 |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -0.7 scores on a scale | Standard Error 0.4 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -1.4 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -1.5 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -1.6 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -1.3 scores on a scale | Standard Error 0.3 |
Comparison: Bowel Domain Scorep-value: 0.31190% CI: [-1.4, 0.3]MMRM
Secondary
Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
Time frame: Week 6
Population: mITT. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6 | 5.1 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6 | 15.0 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6 | 24.8 Percentage of Participants |
Secondary
Induction Phase: Cohort 1: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14
Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.
Time frame: Week 14
Population: mITT. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Induction Phase: Cohort 1: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 1.7 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Induction Phase: Cohort 1: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 13.8 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Induction Phase: Cohort 1: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 8.3 Percentage of Participants |
Secondary
Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14
CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.
Time frame: Baseline and Week 14
Population: mITT. Data evaluable participants are included. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented. Only patients with a baseline score and at least one post-baseline score are included in the analysis
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -2.0 scores on a scale | Standard Error 0.2 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -2.3 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -2.3 scores on a scale | Standard Error 0.2 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -2.2 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -1.9 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -2.0 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -2.0 scores on a scale | Standard Error 0.3 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -1.6 scores on a scale | Standard Error 0.2 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Functional Domain Score | -1.9 scores on a scale | Standard Error 0.2 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 | CD-PRO/SS Bowel Domain Score | -2.3 scores on a scale | Standard Error 0.3 |
Comparison: Functional Domain Scalep-value: 195% CI: [-0.5, 0.9]MMRM
Comparison: Functional Domain Scorep-value: 195% CI: [-0.7, 0.7]MMRM
Comparison: Bowel Domain Scorep-value: 195% CI: [-0.8, 0.9]MMRM
Comparison: Bowel Domain Scorep-value: 195% CI: [-1.1, 0.5]MMRM
Secondary
Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
Time frame: Week 6
Population: mITT. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 | 20.5 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 | 21.3 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 | 20.8 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 | 23.8 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 | 23.4 Percentage of Participants |
p-value: 195% CI: [-8.02, 13.45]Cochran-Mantel-Haenszel
p-value: 0.790895% CI: [-8.78, 12.56]Cochran-Mantel-Haenszel
Secondary
Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14
Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.
Time frame: Week 14
Population: mITT. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 9.9 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 12.3 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 8.7 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 10.2 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14 | 15.3 Percentage of Participants |
p-value: 195% CI: [-6.51, 9.73]Cochran-Mantel-Haenszel
p-value: 0.523595% CI: [-2.24, 15.16]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66
CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.
Time frame: Baseline and Week 66
Population: mITT. Data evaluable participants are included. Only patients with a baseline score and at least one post-baseline score are included in the analysis. The Maintenance Phase Placebo/Placebo arm is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66 | Bowel | -1.7 score on a scale | Standard Error 0.3 |
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66 | Abdominal | -1.4 score on a scale | Standard Error 0.2 |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66 | Bowel | -2.0 score on a scale | Standard Error 0.3 |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66 | Abdominal | -1.7 score on a scale | Standard Error 0.2 |
Comparison: Functional Symptoms Domainp-value: 0.400995% CI: [-0.9, 0.4]MMRM
Comparison: Bowel Symptoms Domainp-value: 0.400995% CI: [-1, 0.4]MMRM
Secondary
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, Among Those Who Achieved Clinical Remission at Week 14
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Induction Phase Cohorts are not included
Time frame: Baseline, Weeks 14 and 66
Population: mITT. Data evaluable participants are included. Placebo/Placebo Maintenance Cohort is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, Among Those Who Achieved Clinical Remission at Week 14 | 39.2 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, Among Those Who Achieved Clinical Remission at Week 14 | 56.5 Percentage of Participants |
p-value: 0.067795% CI: [3.52, 30.27]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Induction Phase Cohorts are not included
Time frame: Baseline and Week 66
Population: mITT. Maintenance Phase Cohorts only. Placebo/Placebo Maintenance Cohort is not reported since this is an exploratory population only. Only patients receiving oral corticosteroids at Baseline are included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline | 11.0 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline | 29.0 Percentage of Participants |
p-value: 0.04895% CI: [11.07, 25.96]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Percentage of participants with clinical remission who will be off corticosteroids for at least 24 weeks prior to Week 66 will be reported. Induction Phase Cohorts are not included
Time frame: Baseline and from Week 14 up to Week 66
Population: mITT. Maintenance Phase Placebo/Placebo is arm is not reported since this is an exploratory population only. Results for Induction Phase is not presented. Only patients receiving oral corticosteroids at Baseline are included in the analysis'
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline | 9.9 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline | 25.8 Percentage of Participants |
p-value: 0.003595% CI: [8.96, 23.31]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Durable Clinical Remission
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Durable clinical remission was defined as clinical remission at ≥4 of the 6 in-clinic assessment visits conducted during the Maintenance Phase at Weeks 24, 28, 32, 44, 56, and 66. Induction Phase Cohorts are not included
Time frame: Week 14 up to Week 66 (assessed at Weeks 24, 28, 32, 44, 56, and 66)
Population: mITT. Maintenance Phase Placebo/Placebo arm is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Durable Clinical Remission | 19.8 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Durable Clinical Remission | 30.9 Percentage of Participants |
p-value: 0.067795% CI: [3.04, 19.24]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 Among Participants Who Achieved Endoscopic Improvement at Week 14
Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Induction Phase Cohorts are not included
Time frame: Baseline, Weeks 14 and 66
Population: mITT. Only patients achieving endoscopic improvement at Week 14 are included in the analysis. Results for Induction Phase Cohort is not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 Among Participants Who Achieved Endoscopic Improvement at Week 14 | 25.3 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 Among Participants Who Achieved Endoscopic Improvement at Week 14 | 37.5 Percentage of Participants |
p-value: 0.12195% CI: [-2.9, 29.94]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score >1, at Week 66
Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.
Time frame: Week 66
Population: mITT. Maintenance Phase Placebo/Placebo are is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Phase - Etrolizumab Responders: Placebo | Maintenance Phase: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score >1, at Week 66 | 5.9 Percentage of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Maintenance Phase: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score >1, at Week 66 | 12.1 Percentage of Participants |
p-value: 0.04895% CI: [0.54, 11.93]Cochran-Mantel-Haenszel
Secondary
Observed Trough Serum Concentration (Ctrough) of Etrolizumab
Serum Etrolizumab Trough Concentration
Time frame: Induction Phase at Weeks 10 and 14, Maintenance Phase at Weeks 16, 24, 28, 32, 44, and 66
Population: mITT. All participants who received at least one dose of study drug and had evaluable PK data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 10 | 9.39 microgram/mL | Standard Deviation 4.59 |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 14 | 10.2 microgram/mL | Standard Deviation 5.27 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 14 | 23.2 microgram/mL | Standard Deviation 10.6 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 10 | 25.1 microgram/mL | Standard Deviation 11.6 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 10 | 10.3 microgram/mL | Standard Deviation 5.07 |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 14 | 11.0 microgram/mL | Standard Deviation 5.04 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 14 | 24.1 microgram/mL | Standard Deviation 11.4 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 10 | 25.7 microgram/mL | Standard Deviation 11.9 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 10 | 9.78 microgram/mL | Standard Deviation 4.63 |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 14 | 10.8 microgram/mL | Standard Deviation 5.43 |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 10 | 25.5 microgram/mL | Standard Deviation 11 |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 14 | 24.6 microgram/mL | Standard Deviation 9.53 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 28 | 7.29 microgram/mL | Standard Deviation 8.45 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 16 | 6.15 microgram/mL | Standard Deviation 4.2 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 24 | 6.58 microgram/mL | Standard Deviation 4.59 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 32 | 7.13 microgram/mL | Standard Deviation 9.76 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 44 | 6.68 microgram/mL | Standard Deviation 3.75 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 66 | 11.7 microgram/mL | Standard Deviation 5.82 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 24 | 8.20 microgram/mL | Standard Deviation 6.34 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 44 | 8.31 microgram/mL | Standard Deviation 6.68 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 16 | 14.8 microgram/mL | Standard Deviation 10.5 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 28 | 8.07 microgram/mL | Standard Deviation 5.81 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 66 | 12.2 microgram/mL | Standard Deviation 6.44 |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Observed Trough Serum Concentration (Ctrough) of Etrolizumab | Week 32 | 7.89 microgram/mL | Standard Deviation 5.96 |
Secondary
Overall Number of Participants Who Develop Malignancies
Participants with malignancies are reported. 'Malignancies are identified by SMQ Malignant and unspecified tumors (narrow)
Time frame: From Baseline up to Week 78
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Develop Malignancies | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Develop Malignancies | 1 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Develop Malignancies | 1 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Develop Malignancies | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Develop Malignancies | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Develop Malignancies | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Develop Malignancies | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Develop Malignancies | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Develop Malignancies | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Develop Malignancies | 2 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Develop Malignancies | 1 Number of Participants |
Secondary
Overall Number of Participants Who Experienced 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)
Investigator text for AEs is coded using MedDRA version 24.0. For participants counts, multiple occurrences of AEs in the same category for an individual are counted only once. For event counts, multiple occurrences of AEs in the same category for an individual are counted separately. Severity Grades from 1 to 5.
Time frame: From Baseline up to Week 78
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced 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) | 50 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced 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) | 83 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced 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) | 82 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced 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) | 120 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced 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) | 115 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced 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) | 51 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced 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) | 95 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced 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) | 85 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced 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) | 42 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced 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) | 190 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced 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) | 189 Number of Participants |
Secondary
Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0
Investigator text for AEs is coded using MedDRA version 24.0. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported.
Time frame: From Baseline up to Week 78
Population: Safety Population. Result data evaluable participants are included
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 2 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 1 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
Secondary
Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0
Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 are reported. 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 indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = Death. The terms 'severe' and 'serious' are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs are counted only once per participant at the highest (worst) grade. Infections are identified by Primary System Organ Class term 'Infections and Infestations'
Time frame: From Baseline up to Week 78
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 8 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 2 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 1 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 10 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 2 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 1 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 17 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 2 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 16 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 24 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 5 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 38 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 23 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 8 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 20 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 1 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 21 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 8 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 7 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 2 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 12 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 25 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 21 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 20 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 2 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 11 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 9 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 44 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 1 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 65 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 11 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 10 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 53 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 42 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 1 Number of Participants |
Secondary
Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event
Investigator text for AEs is coded using MedDRA version 24.0. Infections are identified by primary System Organ Class term 'Infections and Infestations'. The terms 'severe' and 'serious' are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs in the same category for an individual are counted only once
Time frame: From Baseline up to Week 78
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 2 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 4 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 1 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 2 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 5 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 2 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 2 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 1 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 13 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event | 12 Number of Participants |
Secondary
Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0
Investigator test for AEs is coding using MedDRA version 24.0. Injection-Site Reactions are identified by eCRF checkbox for local injection site reactions, and/or primary or secondary HLT Injection Site Reactions. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported.
Time frame: From Baseline up to Week 78
Population: Safety Population. Result data evaluable participants are included
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 4 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 7 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 1 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 3 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 10 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 1 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 8 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 1 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 10 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 6 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 3 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 18 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 4 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 3 | 0 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 2 | 1 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 1 | 8 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 | Grade 5 | 0 Number of Participants |
Secondary
Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Number of participants who discontinued the study due to the adverse events is reported.
Time frame: From Baseline up to Week 78
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 2 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 4 Number of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 1 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 2 Number of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 5 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 2 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 0 Number of Participants |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 0 Number of Participants |
| Maintenance Phase - Placebo Responders: Placebo | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 1 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Placebo | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 1 Number of Participants |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 3 Number of Participants |
Secondary
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result. Induction: treatment groups were pooled across cohorts 1-3. Maintenance: treatment group is stratified by induction dose
Time frame: Baseline, Pre-dose (Hour 0) on Weeks 4, 14, 24, 32, 44, 66 or early termination, 12 weeks after last dose (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, participants for cohorts 1-3 were pooled across each dose arm. For maintenance phase, participants were grouped according to their induction \& maintenance treatment arms
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Placebo | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline with positive ADA | 4.1 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Placebo | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Treatment emergent ADA | 23 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline with positive ADA | 2.8 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Treatment emergent ADA | 22.7 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline with positive ADA | 2.8 Percentage of Participants |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Treatment emergent ADA | 23.1 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline with positive ADA | 5.6 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Treatment emergent ADA | 33.9 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline with positive ADA | 2.8 Percentage of Participants |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Treatment emergent ADA | 33.9 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Baseline with positive ADA | 0 Percentage of Participants |
| Induction Phase - Cohort 3 (Pivotal): Placebo | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab | Treatment emergent ADA | 21.3 Percentage of Participants |