Ulcerative Colitis
Conditions
Brief summary
This two-part, part 1: open-label extension (OLE) and part 2: safety monitoring (SM) study will examine the efficacy and safety of continued etrolizumab treatment in moderate to severe ulcerative colitis (UC) participants previously enrolled in etrolizumab Phase II/III studies. Participants with moderate to severe UC who were enrolled in the Phase II OLE study (GA27927 \[NCT01461317\]) or the Phase III studies (GA28948 \[NCT02163759\], GA28949 \[NCT02171429\], GA28950 \[NCT02100696\], GA29102 \[NCT02165215\], and GA29103 \[NCT02136069\]) were included. Participants from the Phase II OLE study or the Phase III studies who are not eligible or willing to receive etrolizumab in the OLE-SM study, and who have completed the 12-week safety follow-up period will be enrolled in Part 2. Part 1 of OLE-SM will continue for up to 9 years after the first participant is enrolled into the study. Following Part 1, participants will enter Part 2 for a period of 92 weeks.
Interventions
DRUGEtrolizumab
Participants will receive etrolizumab 105 milligrams (mg), administered subcutaneously (SC) every 4 weeks for up to 9 years or until either commercial availability or the Sponsor's decision to terminate the study.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1 (Open-label Extension) \- Participants previously enrolled in the Phase II OLE study or Phase III controlled studies who meet the eligibility criteria for open-label etrolizumab for those studies as described in the protocol Part 2 (Safety Monitoring) * Participants whose safety follow-up or PML follow-up is not completed within Study GA27927 and participants who had their last dose of etrolizumab in July 2016 in Study GA27927 and are not eligible or willing to enroll in Part 1 (OLE) * Participants who participated in one of the etrolizumab Phase III studies and are not eligible or willing to enter Part 1 (OLE) * Participants who transfer from Part 1 (OLE) * Completion of the 12-week safety follow-up prior to entering.
Exclusion criteria
Part 1 (Open-label Extension) * Withdrawal of consent from and participant not compliant in the Phase II OLE study or any of the Phase III studies * Participant who discontinued etrolizumab/etrolizumab placebo prior to Week 10 or did not perform the Week 10 visit of the Phase III Studies GA28948, GA28949, GA29102, and GA29103 * Participant who discontinued etrolizumab/etrolizumab placebo prior to Week 14 or did not perform the Week 14 visit of the Phase III Study GA28950 * Any new, significant, uncontrolled condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 weeks | The pMCS is a composite of 3 assessments, each rated from 0 (none) to 3 (severe disease): stool frequency, rectal bleeding, and physician's global assessment. The total score for pMCS ranges from 0 (none) to 9 (severe disease). pMCS clinical remission was defined as pMCS ≤ 2, a rectal bleeding score of 0-1, physician's global assessment of 0-1, stool frequency subscore of 0-1. Percentages have been rounded off. |
| Part 1: Percentage of Participants With Remission as Determined by the Mayo Clinic Score (MCS) | At OLE Week 108 | The Mayo Clinic scoring system is a composite of 4 assessments for UC disease activity. The 4 component sub-scores are: 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment, each rated from 0-3, 0 representing no pathology to 3 for severe disease. The minimum Mayo Score is 0 (no pathology) and the maximum is 12 (severe disease). MCS remission was defined as MCS ≤ 2, a rectal bleeding score of 0, physician's global assessment of 0-1, stool frequency subscore of 0-1 and endoscopy score of 0-1. Percentage has been rounded off. |
| Part 1: Percentage of Participants With Endoscopic Remission | At OLE Week 108 | The Mayo scoring system is a composite of 4 assessments for UC disease activity. The 4 component sub-scores are: 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment, each rated from 0-3, 0 representing no pathology to 3 for severe disease. The minimum Mayo Score is 0 (no pathology) and the maximum is 12 (severe disease). Endoscopic remission was defined as Mayo Endoscopic subscore = 0. Percentage has been rounded off. |
| Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | An AE is any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v4.0. 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/urgent intervention indicated; Grade 5=Death related to adverse event. |
| Part 1: Number of Participants With Serious Adverse Events (SAEs) | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigation, whether or not considered related to the medicinal (investigational) product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. |
| Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | An AE is any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v4.0. 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/urgent intervention indicated; Grade 5=Death related to adverse event. |
| Part 1: Number of Participants With Serious Infection Related AES | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. |
| Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | AE=untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. Injection-site reaction=any local reaction occurring at the site of injection following study drug administration. Signs (e.g., erythema, induration/swelling at injection site) and symptoms (e.g., pain, pruritus at injection site). Injection site reactions. were graded as per NCI CTCAE v4.0. Grade 1=Tenderness with or without associated symptoms (e.g., warmth, erythema, itching); Grade 2=Pain; lipodystrophy; edema; phlebitis; Grade 3=Ulceration or necrosis; severe tissue damage; operative intervention indicated; Grade 4=life-threatening consequences or urgent intervention indicated; Grade=5 death related to AE. |
| Part 1: Number of Participants With AEs Leading to Etrolizumab Discontinuation | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a Etrolizumab, whether or not considered related to the medicinal (investigational) product. Number of participants who discontinued etrolizumab treatment during the OLE period have been reported here. |
| Part 1: Number of Participants With Malignancies | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Number of participants who developed malignancies during the OLE period have been reported here. |
| Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 | From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years) | AE=untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. Hypersensitivity was assessed as per NCI CTCAE v4.0. 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. |
| Part 2: Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Period | From end of safety follow-up in Part 1 or Phase II/III parent studies up to a maximum of 92 weeks | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Croatia, Czechia, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in this study in 42 countries. All participants who were enrolled in this study previously took part in one of the following parent studies - Phase II: GA27927; Phase III: GA28948, GA28949, GA28950, GA29102, GA29103.
Pre-assignment details
This study consists of two parts, Part 1: Open-label extension (OLE) period and Part 2: Progressive multifocal leukoencephalopathy (PML) safety monitoring (SM) period. A total of 1822 participants with ulcerative colitis (UC) were enrolled in the study, 1773 participants in Part 1 and 796 participants in Part 2. Of the 796, 49 participants were directly enrolled into the Part 2: PML SM period from their respective parent studies.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (OLE): Etrolizumab Only Participants received etrolizumab 105 mg, SC, Q4W for maximum of 369.9 weeks, followed by a 12-week safety follow-up. | 1,026 |
| Part 1 (OLE) to Part 2 (PML SM) Participants received etrolizumab 105 mg, SC, Q4W for maximum of 369.9 weeks, followed by a 12-week safety follow-up in the OLE period. After the OLE period, participants were given the option to enter Part 2 (PML SM). Participants who chose to enter the PML SM period were monitored for PML for a maximum of 92-weeks, during which no etrolizumab treatment was administered. | 747 |
| Part 2 (PML SM) Only Participants from the Phase II or Phase III studies who were not eligible/did not wish to enroll in Part 1 (OLE), and had completed the 12-week safety follow-up period in their parent study were enrolled directly in Part 2 (PML SM). Participants were monitored for PML for a maximum of 92-weeks, during which no etrolizumab treatment was administered. | 49 |
| Total | 1,822 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1: Open Label Extension Period | Adverse Event | 79 | 0 | 0 |
| Part 1: Open Label Extension Period | Death | 9 | 0 | 0 |
| Part 1: Open Label Extension Period | Lost to Follow-up | 53 | 0 | 0 |
| Part 1: Open Label Extension Period | Non-compliance | 12 | 0 | 0 |
| Part 1: Open Label Extension Period | Other | 135 | 0 | 0 |
| Part 1: Open Label Extension Period | Physician Decision | 128 | 0 | 0 |
| Part 1: Open Label Extension Period | Protocol Violation | 1 | 0 | 0 |
| Part 1: Open Label Extension Period | Study Terminated by Sponsor | 29 | 0 | 0 |
| Part 1: Open Label Extension Period | Withdrawal by Subject | 568 | 0 | 0 |
| Part 2: PML Safety Monitoring Period | Adverse Event | 0 | 5 | 0 |
| Part 2: PML Safety Monitoring Period | Death | 0 | 1 | 0 |
| Part 2: PML Safety Monitoring Period | Lost to Follow-up | 0 | 22 | 3 |
| Part 2: PML Safety Monitoring Period | Non-Compliance | 0 | 0 | 1 |
| Part 2: PML Safety Monitoring Period | Physician Decision | 0 | 10 | 1 |
| Part 2: PML Safety Monitoring Period | Reason Not Specified | 0 | 6 | 0 |
| Part 2: PML Safety Monitoring Period | Study Terminated by Sponsor | 0 | 354 | 0 |
| Part 2: PML Safety Monitoring Period | Withdrawal by Subject | 0 | 32 | 1 |
Baseline characteristics
| Characteristic | Part 1 (OLE): Etrolizumab Only | Part 1 (OLE) to Part 2 (PML SM) | Part 2 (PML SM) Only | Total |
|---|---|---|---|---|
| Age, Continuous | 39.7 years STANDARD_DEVIATION 13.3 | 40.7 years STANDARD_DEVIATION 14.1 | 42.7 years STANDARD_DEVIATION 15.2 | 40.2 years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 93 Participants | 0 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 915 Participants | 632 Participants | 47 Participants | 1594 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 52 Participants | 22 Participants | 2 Participants | 76 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 101 Participants | 40 Participants | 4 Participants | 145 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 18 Participants | 0 Participants | 29 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 36 Participants | 32 Participants | 2 Participants | 70 Participants |
| Race/Ethnicity, Customized Unknown | 33 Participants | 20 Participants | 2 Participants | 55 Participants |
| Race/Ethnicity, Customized White | 843 Participants | 635 Participants | 40 Participants | 1518 Participants |
| Sex: Female, Male Female | 417 Participants | 333 Participants | 23 Participants | 773 Participants |
| Sex: Female, Male Male | 609 Participants | 414 Participants | 26 Participants | 1049 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 1,773 | 1 / 796 |
| other Total, other adverse events | 1,052 / 1,773 | 2 / 796 |
| serious Total, serious adverse events | 373 / 1,773 | 2 / 796 |
Outcome results
Primary
Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0]
An AE is any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v4.0. 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/urgent intervention indicated; Grade 5=Death related to adverse event.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | Any AEs | 1431 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | Grade 1 AEs | 315 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | Grade 2 AEs | 679 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | Grade 3 AEs | 405 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | Grade 4 AEs | 23 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events (AEs) and Severity of AEs Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.0] | Grade 5 AEs | 9 Participants |
Primary
Part 1: Number of Participants With AEs Leading to Etrolizumab Discontinuation
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a Etrolizumab, whether or not considered related to the medicinal (investigational) product. Number of participants who discontinued etrolizumab treatment during the OLE period have been reported here.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With AEs Leading to Etrolizumab Discontinuation | 234 Participants |
Primary
Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0
AE=untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. Hypersensitivity was assessed as per NCI CTCAE v4.0. 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.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 | Hypersensitivity Reactions, Any Grade | 85 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 | Hypersensitivity Reactions, Grade 1 | 65 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 | Hypersensitivity Reactions, Grade 2 | 19 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 | Hypersensitivity Reactions, Grade 3 | 4 Participants |
Primary
Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0
An AE is any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v4.0. 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/urgent intervention indicated; Grade 5=Death related to adverse event.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | Infection Related AEs, Any Grade | 825 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | Infection Related AEs, Grade 1 | 576 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | Infection Related AEs, Grade 2 | 423 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | Infection Related AEs, Grade 3 | 96 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | Infection Related AEs, Grade 4 | 6 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 | Infection Related AEs, Grade 5 | 1 Participants |
Primary
Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0
AE=untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. Injection-site reaction=any local reaction occurring at the site of injection following study drug administration. Signs (e.g., erythema, induration/swelling at injection site) and symptoms (e.g., pain, pruritus at injection site). Injection site reactions. were graded as per NCI CTCAE v4.0. Grade 1=Tenderness with or without associated symptoms (e.g., warmth, erythema, itching); Grade 2=Pain; lipodystrophy; edema; phlebitis; Grade 3=Ulceration or necrosis; severe tissue damage; operative intervention indicated; Grade 4=life-threatening consequences or urgent intervention indicated; Grade=5 death related to AE.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | Injection Site Reactions, Grade 5 | 0 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | Injection Site Reactions, Any Grade | 32 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | Injection Site Reactions, Grade 1 | 28 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | Injection Site Reactions, Grade 2 | 5 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | Injection Site Reactions, Grade 3 | 0 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | Injection Site Reactions, Grade 4 | 0 Participants |
Primary
Part 1: Number of Participants With Malignancies
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Number of participants who developed malignancies during the OLE period have been reported here.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Malignancies | 38 Participants |
Primary
Part 1: Number of Participants With Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigation, whether or not considered related to the medicinal (investigational) product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Serious Adverse Events (SAEs) | 373 Participants |
Primary
Part 1: Number of Participants With Serious Infection Related AES
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 7 years)
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Serious Infection Related AES | 110 Participants |
Primary
Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS)
The pMCS is a composite of 3 assessments, each rated from 0 (none) to 3 (severe disease): stool frequency, rectal bleeding, and physician's global assessment. The total score for pMCS ranges from 0 (none) to 9 (severe disease). pMCS clinical remission was defined as pMCS ≤ 2, a rectal bleeding score of 0-1, physician's global assessment of 0-1, stool frequency subscore of 0-1. Percentages have been rounded off.
Time frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 weeks
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Baseline | 32.0 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 4 | 47.2 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 8 | 52.2 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 12 | 55.9 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 24 | 63.7 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 36 | 68.3 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 48 | 73.4 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 60 | 72.2 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 72 | 75.4 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 84 | 76.5 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 96 | 77.2 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 108 | 72.0 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 120 | 77.4 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 132 | 82.2 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 144 | 80.0 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 156 | 78.5 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 168 | 81.0 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 180 | 78.8 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 192 | 80.8 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 204 | 83.6 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 216 | 84.8 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 228 | 85.1 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 240 | 82.6 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 252 | 86.0 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 264 | 84.8 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 276 | 86.0 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 288 | 82.4 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 300 | 86.7 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 312 | 87.1 percentage of participants |
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) | Week 324 | 80.0 percentage of participants |
Primary
Part 1: Percentage of Participants With Endoscopic Remission
The Mayo scoring system is a composite of 4 assessments for UC disease activity. The 4 component sub-scores are: 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment, each rated from 0-3, 0 representing no pathology to 3 for severe disease. The minimum Mayo Score is 0 (no pathology) and the maximum is 12 (severe disease). Endoscopic remission was defined as Mayo Endoscopic subscore = 0. Percentage has been rounded off.
Time frame: At OLE Week 108
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Endoscopic Remission | 45.7 percentage of participants |
Primary
Part 1: Percentage of Participants With Remission as Determined by the Mayo Clinic Score (MCS)
The Mayo Clinic scoring system is a composite of 4 assessments for UC disease activity. The 4 component sub-scores are: 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment, each rated from 0-3, 0 representing no pathology to 3 for severe disease. The minimum Mayo Score is 0 (no pathology) and the maximum is 12 (severe disease). MCS remission was defined as MCS ≤ 2, a rectal bleeding score of 0, physician's global assessment of 0-1, stool frequency subscore of 0-1 and endoscopy score of 0-1. Percentage has been rounded off.
Time frame: At OLE Week 108
Population: OLE Population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Percentage of Participants With Remission as Determined by the Mayo Clinic Score (MCS) | 58.1 percentage of participants |
Primary
Part 2: Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Period
Time frame: From end of safety follow-up in Part 1 or Phase II/III parent studies up to a maximum of 92 weeks
Population: PML Safety Monitoring population included all participants who entered the PML SM period. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent studies have been reported together.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 2: Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Period | 0 Participants |