Ulcerative Colitis, Crohn's Disease
Conditions
Brief summary
This study will evaluate pharmacokinetics, pharmacodynamics and safety of etrolizumab in pediatric patients of 4 to \<18 years of age with moderate to severe ulcerative colitis (UC) or with moderate to severe Crohn's disease (CD).
Interventions
DRUGEtrolizumab
Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age of 4 years to \<18 years at the time of signing the Informed Consent Form. * Weight of 13 kilograms (kg) or more * Diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) confirmed by biopsy and established for ≥3 months (i.e., after first diagnosis by a physician according to American College of Gastroenterology \[ACG\] guidelines) prior to screening * Inadequate response, loss of response or intolerance to prior immunosuppressants and/or corticosteroid treatment and/or anti-tumor necrosis factor (TNF) therapy * For postpubertal females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 24 weeks after the last dose of etrolizumab. * For male patients: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Exclusion criteria
* Pregnant or lactating * Lack of peripheral venous access * Congenital or acquired immune deficiency * Neurological conditions or diseases that may interfere with monitoring for progressive multifocal leukoencephalopathy (PML) * History of demyelinating disease * History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Arm Etro Q4W: Predose on Days 28, 56, 84, 112 and Arm Etro Q8W: Predose on Days 56, 112 | Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. |
| Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56 | Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters. |
| Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | Arm Etro Q4W: Days 1, 84 and Arm Etro Q8W: Days 1, 56 | Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters. |
| Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase | Arm Etro Q4W: Days 56, 84, 88, 98, 112 and Arm Etro Q8W: Day 56, 60, 70, 84, 88, 98, 112 | Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters. |
| Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase | Arm Etro Q4W: Days 84, 88, 98, 112, 126, 140, 168 and Arm Etro Q8W: Days 56, 60, 70, 84, 88, 98, 112, 126, 140, 168 | Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters. |
| Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | Predose (dosing days only) at Baseline (Day 1) and on Days 4, 56, 84, 98, and 112 (Treatment Period), and Days 126, 140, and 168 (Follow-Up Period) | Target engagement of etrolizumab was assessed via measurement of Beta7 receptor occupancy on Beta7 receptor-expressing gut homing lymphocyte subsets in peripheral blood, including CD3, CD4, and CD8 T cells and CD19 B cells, using qualified flow cytometry methods. A decrease to 0% of baseline (BL) in median absolute cell counts of Beta7 receptor-expressing T and B cell subsets with unoccupied Beta7 receptors following etrolizumab treatment indicated maximal receptor occupancy by etrolizumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events | OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks | Serious infection-related AEs were assessed using NCI-CTCAE v4.0. |
| Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions | OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks | Hypersensitivity reactions were assessed using NCI-CTCAE v4.0. |
| Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks) | All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. |
| Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Predose (dosing days only) at Baseline (Day 1), Days 28, 84, and 112, Weeks 24, 36, 72, and 120, and every 12 weeks thereafter for up to 4.25 years | Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative). |
| Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase | PML Period: After completion of safety follow up in Randomized Treatment period or after completion of safety follow up after OLE treatment, up to approximately 92 weeks | The safety surveillance PML-monitoring phase (no etrolizumab treatment) consisted of telephone calls approximately every 6 months with administration of the protocol's PML Subjective Checklist. If there were any signs or symptoms suggestive of PML identified on this subjective checklist during the telephone call, the participant was asked to come into the clinic for a neurologic examination. The protocol's PML Algorithm was followed for any suspected case of PML, and any confirmed case of PML would be reported as a serious adverse event. |
| Long-Term Safety of Etrolizumab: Number of Participants With Malignancies | OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks | Malignancies were assessed using NCI-CTCAE v4.0. |
| Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase | From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks) | Serious infection-related AEs were assessed using NCI-CTCAE v4.0. |
| Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase | From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks) | Hypersensitivity reactions were assessed using NCI-CTCAE v4.0. |
| Number of Participants With Malignancies During the Randomized Treatment Phase | From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks) | Malignancies were assessed using NCI-CTCAE v4.0. |
| Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Predose (dosing days only) on Days 1, 28, 84, 112, and 168 (up to the end of the randomized treatment phase at Week 24) | Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative). |
| Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks | All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. |
Countries
Belgium, Poland, Spain, United Kingdom
Participant flow
Pre-assignment details
The study was conducted in 3 parts: Randomized Treatment Period, Open-label Extension (OLE) Period and Progressive Multifocal Leukoencephalopathy (PML) Safety Monitoring (SM) Period. Participants who completed the randomized treatment period were given the option to continue treatment in OLE period. After the randomized treatment period (if they did not enter OLE) or after the OLE period, participants were given the option to continue in PML SM period during which they were monitored for PML.
Participants by arm
| Arm | Count |
|---|---|
| Etrolizumab Q4W Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up). | 12 |
| Etrolizumab Q8W Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up). | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open Label Extension Period | Adverse Event | 0 | 0 | 4 | 0 |
| Open Label Extension Period | Lack of Efficacy | 0 | 0 | 8 | 0 |
| Open Label Extension Period | Reason Not Provided | 0 | 0 | 1 | 0 |
| Open Label Extension Period | Study Terminated by Sponsor | 0 | 0 | 6 | 0 |
| Open Label Extension Period | Withdrawal by Subject | 0 | 0 | 2 | 0 |
| PML Safety Monitoring Period | Study Terminated by Sponsor | 0 | 0 | 0 | 9 |
| Randomized Treatment Period | Adverse Event | 1 | 0 | 0 | 0 |
| Randomized Treatment Period | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Etrolizumab Q8W | Etrolizumab Q4W | Total |
|---|---|---|---|
| Age, Continuous | 13.42 Years STANDARD_DEVIATION 4.46 | 12.25 Years STANDARD_DEVIATION 3.62 | 12.83 Years STANDARD_DEVIATION 4.02 |
| Disease Indication: Crohn's Disease or Ulcerative Colitis Crohn's Disease | 5 Participants | 5 Participants | 10 Participants |
| Disease Indication: Crohn's Disease or Ulcerative Colitis Ulcerative Colitis | 7 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 12 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 12 Participants | 24 Participants |
| Randomization Stratification Factor: Body Weight <40 kg or ≥40 kg <40 kg | 4 Participants | 5 Participants | 9 Participants |
| Randomization Stratification Factor: Body Weight <40 kg or ≥40 kg ≥40 kg | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 21 | 0 / 13 |
| other Total, other adverse events | 8 / 12 | 9 / 12 | 20 / 21 | 4 / 13 |
| serious Total, serious adverse events | 2 / 12 | 2 / 12 | 6 / 21 | 0 / 13 |
Outcome results
Primary
Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Time frame: Arm Etro Q4W: Days 56, 84, 88, 98, 112 and Arm Etro Q8W: Day 56, 60, 70, 84, 88, 98, 112
Population: Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their last dose of study drug (on Day 56 for Q8W arm and Day 84 for Q4W arm).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab Q4W | Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase | AUC84-112 | 167 Day*μg/mL | Standard Deviation 86.9 |
| Etrolizumab Q8W | Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase | AUC56-112 | 521 Day*μg/mL | Standard Deviation 306 |
Primary
Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Time frame: Arm Etro Q4W: Days 84, 88, 98, 112, 126, 140, 168 and Arm Etro Q8W: Days 56, 60, 70, 84, 88, 98, 112, 126, 140, 168
Population: Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their last dose of study drug (on Day 56 for Q8W arm and Day 84 for Q4W arm).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etrolizumab Q4W | Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase | 7.31 Day | Standard Deviation 1.76 |
| Etrolizumab Q8W | Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase | 8.65 Day | Standard Deviation 3.74 |
Primary
Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Time frame: Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56
Population: Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their first dose (Day 1 for both arms) and last dose (on Day 56 for Q8W arm and Day 84 for Q4W arm) of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab Q4W | Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After First Dose (Day 1) | 7.73 micrograms per millilitre (μg/mL) | Standard Deviation 2.18 |
| Etrolizumab Q4W | Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After Last Dose (Q4W Day 84, Q8WDay 56) | 9.80 micrograms per millilitre (μg/mL) | Standard Deviation 4.86 |
| Etrolizumab Q8W | Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After First Dose (Day 1) | 19.0 micrograms per millilitre (μg/mL) | Standard Deviation 8.21 |
| Etrolizumab Q8W | Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After Last Dose (Q4W Day 84, Q8WDay 56) | 18.1 micrograms per millilitre (μg/mL) | Standard Deviation 6.25 |
Primary
Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase
Target engagement of etrolizumab was assessed via measurement of Beta7 receptor occupancy on Beta7 receptor-expressing gut homing lymphocyte subsets in peripheral blood, including CD3, CD4, and CD8 T cells and CD19 B cells, using qualified flow cytometry methods. A decrease to 0% of baseline (BL) in median absolute cell counts of Beta7 receptor-expressing T and B cell subsets with unoccupied Beta7 receptors following etrolizumab treatment indicated maximal receptor occupancy by etrolizumab.
Time frame: Predose (dosing days only) at Baseline (Day 1) and on Days 4, 56, 84, 98, and 112 (Treatment Period), and Days 126, 140, and 168 (Follow-Up Period)
Population: Pharmacodynamics (PD) Evaluable Population: all participants who received at least one dose of study treatment and had evaluable PD data.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 168 | 71.64 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 22.4 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 168 | 74.49 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 26.1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 4 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 98 | 0.36 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0.4 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 56 | 1.56 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1.6 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 4 | 0.17 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0.2 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 84 | 2.72 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 2.7 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 56 | 1.92 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1.9 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 98 | 1.10 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1.1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 112 | 4.06 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 2.6 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 112 | 0.97 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 56 | 3.33 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 3.3 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 126 | 20.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 20 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 168 | 73.21 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 17.7 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 140 | 54.17 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 18.8 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 84 | 7.14 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 7.1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 168 | 63.34 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 40.1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 126 | 12.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 12 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 98 | 0.24 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0.2 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 4 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 4 | 0.18 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0.2 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 56 | 3.57 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 3.6 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 112 | 3.60 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 3.1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 84 | 10.71 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 10.7 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 140 | 47.47 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 21.9 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 98 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 126 | 13.33 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 13.3 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 112 | 7.14 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 7.1 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 84 | 7.43 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 6 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 126 | 42.86 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 21.4 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 140 | 55.34 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 23.9 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 140 | 68.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 30.5 |
| Etrolizumab Q4W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 140 | 77.78 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 32.6 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 4 | 0.40 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0.4 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 56 | 13.74 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 13.5 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 84 | 1.06 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 98 | 1.06 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 112 | 6.01 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 5.6 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 126 | 27.24 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 24.6 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 140 | 56.82 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 22.2 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD3 T Cells: Day 168 | 51.79 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 23.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 4 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 168 | 40.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 13.2 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 56 | 16.56 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 16.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 84 | 1.28 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 98 | 1.28 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 1.3 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 112 | 6.74 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 6.4 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 126 | 37.03 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 33.7 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 140 | 62.01 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 20.3 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD4 T Cells: Day 168 | 50.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 16.3 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 4 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 56 | 8.41 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 8.4 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 84 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 98 | 2.33 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 2.3 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 112 | 2.46 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 2.5 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 126 | 14.51 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 14.5 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 140 | 40.98 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 24.7 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD8 T Cells: Day 168 | 55.56 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 21.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Baseline | 100 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 4 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 56 | 19.14 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 17.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 84 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 98 | 0.00 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 0 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 112 | 7.14 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 7.1 |
| Etrolizumab Q8W | Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase | CD19 B Cells: Day 126 | 33.93 Percentage of BL Unoccupied Beta7 Cells | Standard Deviation 32.3 |
Primary
Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method.
Time frame: Arm Etro Q4W: Predose on Days 28, 56, 84, 112 and Arm Etro Q8W: Predose on Days 56, 112
Population: Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants at the end of each dosing interval (on Days 28, 56, 84, and 112 for Q4W arm and Days 56 and 112 for Q8W arm).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab Q4W | Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Day 28 | 1.87 micrograms per millilitre (μg/mL) | Standard Deviation 1.32 |
| Etrolizumab Q4W | Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Day 112 | 2.79 micrograms per millilitre (μg/mL) | Standard Deviation 2.01 |
| Etrolizumab Q4W | Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Day 56 | 3.22 micrograms per millilitre (μg/mL) | Standard Deviation 2.24 |
| Etrolizumab Q4W | Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Day 84 | 3.00 micrograms per millilitre (μg/mL) | Standard Deviation 2.38 |
| Etrolizumab Q8W | Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Day 56 | 1.82 micrograms per millilitre (μg/mL) | Standard Deviation 1.99 |
| Etrolizumab Q8W | Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase | Day 112 | 3.70 micrograms per millilitre (μg/mL) | Standard Deviation 4.64 |
Primary
Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Time frame: Arm Etro Q4W: Days 1, 84 and Arm Etro Q8W: Days 1, 56
Population: Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their first dose (Day 1 for both arms) and last dose (on Day 56 for Q8W arm and Day 84 for Q4W arm) of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etrolizumab Q4W | Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After First Dose (Day 1) | 4.65 Day | Standard Deviation 1.43 |
| Etrolizumab Q4W | Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After Last Dose (Q4W Day 84, Q8WDay 56) | 5.04 Day | Standard Deviation 2.92 |
| Etrolizumab Q8W | Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After First Dose (Day 1) | 4.00 Day | Standard Deviation 1.48 |
| Etrolizumab Q8W | Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase | After Last Dose (Q4W Day 84, Q8WDay 56) | 4.94 Day | Standard Deviation 3.28 |
Secondary
Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0
All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Population: Safety Population: all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Any Grade | 20 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 1 | 0 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 2 | 12 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 3 | 8 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 4 | 0 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 5 | 0 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 4 | 0 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Any Grade | 4 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 3 | 0 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 1 | 2 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 5 | 0 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 | Any Adverse Event - Grade 2 | 2 Participants |
Secondary
Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline
Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative).
Time frame: Predose (dosing days only) at Baseline (Day 1), Days 28, 84, and 112, Weeks 24, 36, 72, and 120, and every 12 weeks thereafter for up to 4.25 years
Population: ADA Evaluable Population: all participants who received at least one dose of study treatment and had at least one baseline or post-baseline ADA result from at least one sample.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Baseline (BL): ADA Positive | 1 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | BL: ADA Negative | 11 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Post-BL: Treatment-Emergent ADA Positive | 4 Participants |
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Post-BL: Treatment-Emergent ADA Negative | 7 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Post-BL: Treatment-Emergent ADA Negative | 9 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Baseline (BL): ADA Positive | 0 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | Post-BL: Treatment-Emergent ADA Positive | 3 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline | BL: ADA Negative | 12 Participants |
Secondary
Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions
Hypersensitivity reactions were assessed using NCI-CTCAE v4.0.
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions | 4 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions | 1 Participants |
Secondary
Long-Term Safety of Etrolizumab: Number of Participants With Malignancies
Malignancies were assessed using NCI-CTCAE v4.0.
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Malignancies | 0 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Malignancies | 0 Participants |
Secondary
Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events
Serious infection-related AEs were assessed using NCI-CTCAE v4.0.
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events | 1 Participants |
| Etrolizumab Q8W | Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events | 0 Participants |
Secondary
Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase
All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Population: Safety Population: all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etrolizumab Q4W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Any Grade | 9 Participants |
| Etrolizumab Q4W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 1 | 2 Participants |
| Etrolizumab Q4W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 2 | 4 Participants |
| Etrolizumab Q4W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 3 | 3 Participants |
| Etrolizumab Q4W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 4 | 0 Participants |
| Etrolizumab Q4W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 5 | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 4 | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Any Grade | 10 Participants |
| Etrolizumab Q8W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 3 | 3 Participants |
| Etrolizumab Q8W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 1 | 2 Participants |
| Etrolizumab Q8W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 5 | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase | Any Adverse Event - Grade 2 | 5 Participants |
Secondary
Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase
Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative).
Time frame: Predose (dosing days only) on Days 1, 28, 84, 112, and 168 (up to the end of the randomized treatment phase at Week 24)
Population: ADA Evaluable Population: all participants who received at least one dose of study treatment and had at least one baseline or post-baseline ADA result from at least one sample.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etrolizumab Q4W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Baseline (BL): ADA Positive | 1 Participants |
| Etrolizumab Q4W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | BL: ADA Negative | 11 Participants |
| Etrolizumab Q4W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Post-BL: Treatment-Emergent ADA Positive | 4 Participants |
| Etrolizumab Q4W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Post-BL: Treatment-Emergent ADA Negative | 7 Participants |
| Etrolizumab Q8W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Post-BL: Treatment-Emergent ADA Negative | 10 Participants |
| Etrolizumab Q8W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Baseline (BL): ADA Positive | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | Post-BL: Treatment-Emergent ADA Positive | 2 Participants |
| Etrolizumab Q8W | Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase | BL: ADA Negative | 12 Participants |
Secondary
Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase
The safety surveillance PML-monitoring phase (no etrolizumab treatment) consisted of telephone calls approximately every 6 months with administration of the protocol's PML Subjective Checklist. If there were any signs or symptoms suggestive of PML identified on this subjective checklist during the telephone call, the participant was asked to come into the clinic for a neurologic examination. The protocol's PML Algorithm was followed for any suspected case of PML, and any confirmed case of PML would be reported as a serious adverse event.
Time frame: PML Period: After completion of safety follow up in Randomized Treatment period or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase | 0 Participants |
Secondary
Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase
Hypersensitivity reactions were assessed using NCI-CTCAE v4.0.
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase | 0 Participants |
Secondary
Number of Participants With Malignancies During the Randomized Treatment Phase
Malignancies were assessed using NCI-CTCAE v4.0.
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Number of Participants With Malignancies During the Randomized Treatment Phase | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Malignancies During the Randomized Treatment Phase | 0 Participants |
Secondary
Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase
Serious infection-related AEs were assessed using NCI-CTCAE v4.0.
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etrolizumab Q4W | Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase | 0 Participants |
| Etrolizumab Q8W | Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase | 0 Participants |