Crohn Disease
Conditions
Brief summary
This open-label extension and safety monitoring study is composed of two parts: Part 1 will evaluate the long-term safety and efficacy of continued etrolizumab treatment in participants with moderately to severely active Crohn's disease who were previously enrolled in the etrolizumab Phase III Study GA29144 (NCT02394028) and who meet eligibility criteria for enrollment into Part 1. In Part 2, participants who have stopped etrolizumab treatment (either by exiting Part 1 of this study or by entering directly from Study GA29144 \[NCT02394028\]) will be monitored for 92 weeks for progressive multifocal leukoencephalopathy (PML) and other safety events.
Interventions
DRUGEtrolizumab
105 mg etrolizumab subcutaneous administration once every 4 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
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: * Patients previously enrolled in etrolizumab Phase III study GA29144 (NCT02394028) who meet the eligibility criteria for open-label etrolizumab as described in the protocol Part 2 Safety Monitoring: * Patients who participated in etrolizumab Phase III study GA29144 (NCT02394028) and are not eligible or choose not to enter Part 1 * Patients who transfer from Part 1 * Completion of the 12-week safety follow-up period prior to entering
Exclusion criteria
Part 1 Open-Label Extension: * Any new, significant, uncontrolled condition Part 2 Safety Monitoring: * No
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Day 1 and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240 and 252 of OLE | CDAI is a score obtained from composite of eight assessments: number of liquid or soft stools, abdominal pain, general well-being, presence of complications, taking lomotil (diphenoxylate/atropine) or other opiates for diarrhea, presence of an abdominal mass, hematocrit, and percentage deviation from standard weight. A decrease in CDAI over time indicates improvement in disease activity. CDAI scores range from 0 to 600. A higher score indicates worse outcome. A total score of less than 150 corresponds to remission. |
| Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Day 1 and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240 and 252 of OLE | Clinical remission was defined as a liquid/soft stool frequency (SF) mean daily score ≤3 and an abdominal pain (AP) mean daily score ≤1 with no worsening in either subscore compared to baseline, where the average was taken over 7 days prior to visit. Abdominal pain severity was assessed using the abdominal pain questionnaire which is an 11-point numeric rating scale with score ranging from 0 (no pain) to 10 (worse pain). Liquid/soft stool frequency was reported using the bristol stool form scale which classifies stools into seven groups based on its consistency i.e., type 1- separate hard lumps, type 2- sausage-shaped but lumpy, type 3- like a sausage but with cracks on the surface, type 4- like a sausage or snake, smooth and soft, type 5- soft blobs with clear-cut edges, type 6- fluffy pieces with ragged edges and type 7- entirely liquid with no solid pieces. |
| Part 1: Number of Participants With Improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 108 | At OLE Week 108 | SES-CD is an endoscopic score composite of 4 variables (ulcers size, percentage of ulcerated surface, inflamed surface, and presence of narrowing) in up to 5 ileocolonic segments (ileum right, colon, transverse colon, left colon, rectum) and scored on a scale of 0-3, with total score from 0-60. Higher score indicates higher ulcer surface/size in the 4 variables. Endoscopic improvement was defined as ≥50% reduction in SES-CD score compared to baseline. |
| Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as 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 6.3 years) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. 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 AE. Multiple occurrences of AEs in the same category at the worst (highest) NCIC-CTCAE grade for an individual are counted only once. |
| 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 6.3 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 6.3 years) | AE=untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. AEs were graded 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. If a participant experienced multiple occurrences of AEs at different grades, they were counted in each grade where they had at least one AE of that grade. |
| Part 1: Incidence Rate of Infection-related Adverse Event | From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a 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. AE rate (per 100 participant years) = \[Total number of AEs (in OLE only) / Total number of participant years at risk (in OLE only)\]\*100. Total participant-years at risk is the sum over all participants of the time intervals (in years) from the first dose of study treatment in Part 1 (OLE) until the participant completes/withdraws from the study (including the 12-week safety follow-up, if applicable). |
| 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 6.3 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 Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 | From Day 1 up to end of safety 12-week follow-up in OLE (approximately 6.3 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 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 Adverse Events Leading to Etrolizumab Discontinuation | From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a 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 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 6.3 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: Incidence Rate of Malignancies | From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) | Malignancy rate (per 100 participant years) = \[Total number of malignancies (in OLE only) / Total number of participant years at risk (in OLE only)\]\*100. Total participant-years at risk is the sum over all participants of the time intervals (in years) from the first dose of study treatment in Part 1 (OLE) until the participant completes/withdraws from the study (including the 12-week safety follow-up, if applicable). |
| 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 6.3 years) | Hypersensitivity was reported using the MedDRA anaphylactic reaction standard MedDRA query (SMQ) and Sampson's criteria. 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 or Suspected Progressive Multifocal Leukoencephalopathy (PML) | From end of safety follow-up in Part 1 or study GA29144 up to maximum of 92 weeks | PML was assessed by the PML Subjective Checklist (symptom assessment) and the PML Objective Checklist (neurologic evaluation). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czechia, Estonia, France, Germany, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in this study in 33 countries. All participants who enrolled into this study previously took part in study GA29144 (NCT02394028).
Pre-assignment details
This study consists of 2 parts, Part 1: Open-label extension (OLE) period & Part 2: Progressive multifocal leukoencephalopathy (PML) safety monitoring (SM) period. A total of 790 participants were enrolled in the study, 751 participants in Part 1 and 359 participants in Part 2. Of the 359, 39 participants directly entered into the Part 2 PML SM period from study GA29144.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (OLE): Etrolizumab Only Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up. | 431 |
| Part 1 (OLE) to Part 2 (PML SM) Participants received etrolizumab 105 mg, SC, Q4W for maximum of 320 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. | 320 |
| Part 2 (PML SM) Only Participants from study GA29144 who completed the 12-week safety follow-up period and were not eligible/did not wish to enroll in the Part 1 (OLE), enrolled directly in Part 2 (PML SM). Participant were monitored for PML for a maximum of 92-weeks, during which no etrolizumab treatment was administered. | 39 |
| Total | 790 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1: Open Label Extension Period | Adverse Event | 26 | 0 | 0 |
| Part 1: Open Label Extension Period | Death | 3 | 0 | 0 |
| Part 1: Open Label Extension Period | Lost to Follow-up | 23 | 0 | 0 |
| Part 1: Open Label Extension Period | Non-Compliance | 2 | 0 | 0 |
| Part 1: Open Label Extension Period | Other | 1 | 0 | 0 |
| Part 1: Open Label Extension Period | Physician Decision | 61 | 0 | 0 |
| Part 1: Open Label Extension Period | Reason Not Specified | 59 | 0 | 0 |
| Part 1: Open Label Extension Period | Study Terminated By Sponsor | 19 | 0 | 0 |
| Part 1: Open Label Extension Period | Withdrawal by Subject | 232 | 0 | 0 |
| Part 2: PML Safety Monitoring Period | Adverse Event | 0 | 4 | 0 |
| Part 2: PML Safety Monitoring Period | Death | 0 | 1 | 0 |
| Part 2: PML Safety Monitoring Period | Lost to Follow-up | 0 | 9 | 3 |
| Part 2: PML Safety Monitoring Period | Non-Compliance | 0 | 1 | 0 |
| Part 2: PML Safety Monitoring Period | Other | 0 | 1 | 0 |
| Part 2: PML Safety Monitoring Period | Physician Decision | 0 | 7 | 0 |
| Part 2: PML Safety Monitoring Period | Reason Not Specified | 0 | 6 | 1 |
| Part 2: PML Safety Monitoring Period | Study Terminated By Sponsor | 0 | 167 | 0 |
| Part 2: PML Safety Monitoring Period | Withdrawal by Subject | 0 | 12 | 2 |
Baseline characteristics
| Characteristic | Part 1 (OLE): Etrolizumab Only | Part 1 (OLE) to Part 2 (PML SM) | Part 2 (PML SM) Only | Total |
|---|---|---|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 13 | 39.7 years STANDARD_DEVIATION 13.6 | 36.8 years STANDARD_DEVIATION 13 | 38.5 years STANDARD_DEVIATION 13.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 24 Participants | 3 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 385 Participants | 280 Participants | 35 Participants | 700 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants | 16 Participants | 1 Participants | 39 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 25 Participants | 8 Participants | 2 Participants | 35 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 10 Participants | 2 Participants | 27 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 6 Participants | 1 Participants | 17 Participants |
| Race/Ethnicity, Customized Unknown | 21 Participants | 14 Participants | 1 Participants | 36 Participants |
| Race/Ethnicity, Customized White | 358 Participants | 277 Participants | 33 Participants | 668 Participants |
| Sex: Female, Male Female | 199 Participants | 158 Participants | 19 Participants | 376 Participants |
| Sex: Female, Male Male | 232 Participants | 162 Participants | 20 Participants | 414 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 751 | 1 / 359 |
| other Total, other adverse events | 453 / 751 | 2 / 359 |
| serious Total, serious adverse events | 206 / 751 | 1 / 359 |
Outcome results
Primary
Part 1: Incidence Rate of Infection-related Adverse Event
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a 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. AE rate (per 100 participant years) = \[Total number of AEs (in OLE only) / Total number of participant years at risk (in OLE only)\]\*100. Total participant-years at risk is the sum over all participants of the time intervals (in years) from the first dose of study treatment in Part 1 (OLE) until the participant completes/withdraws from the study (including the 12-week safety follow-up, if applicable).
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Incidence Rate of Infection-related Adverse Event | 62.74 event per 100 participant-years |
Primary
Part 1: Incidence Rate of Malignancies
Malignancy rate (per 100 participant years) = \[Total number of malignancies (in OLE only) / Total number of participant years at risk (in OLE only)\]\*100. Total participant-years at risk is the sum over all participants of the time intervals (in years) from the first dose of study treatment in Part 1 (OLE) until the participant completes/withdraws from the study (including the 12-week safety follow-up, if applicable).
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Incidence Rate of Malignancies | 1.85 events per 100-participant-years |
Primary
Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as 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 a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. 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 AE. Multiple occurrences of AEs in the same category at the worst (highest) NCIC-CTCAE grade for an individual are counted only once.
Time frame: From Day 1 up to end of 12-week safety follow-up in OLE (approximately 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | AEs, Any Grade | 624 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | Grade 1 AEs | 121 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | Grade 2 AEs | 259 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | Grade 3 AEs | 214 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | Grade 4 AEs | 27 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) | Grade 5 AEs | 3 Participants |
Primary
Part 1: Number of Participants With Adverse Events Leading to Etrolizumab Discontinuation
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a 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 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 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Adverse Events Leading to Etrolizumab Discontinuation | 112 Participants |
Primary
Part 1: Number of Participants With Clinical Remission at 12-week Intervals
Clinical remission was defined as a liquid/soft stool frequency (SF) mean daily score ≤3 and an abdominal pain (AP) mean daily score ≤1 with no worsening in either subscore compared to baseline, where the average was taken over 7 days prior to visit. Abdominal pain severity was assessed using the abdominal pain questionnaire which is an 11-point numeric rating scale with score ranging from 0 (no pain) to 10 (worse pain). Liquid/soft stool frequency was reported using the bristol stool form scale which classifies stools into seven groups based on its consistency i.e., type 1- separate hard lumps, type 2- sausage-shaped but lumpy, type 3- like a sausage but with cracks on the surface, type 4- like a sausage or snake, smooth and soft, type 5- soft blobs with clear-cut edges, type 6- fluffy pieces with ragged edges and type 7- entirely liquid with no solid pieces.
Time frame: Day 1 and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240 and 252 of OLE
Population: OLE population included all participants who received at least one dose of study drug in Study GA29145 Part 1 (OLE). Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Day 1 | 200 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 12 | 161 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 24 | 168 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 36 | 162 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 48 | 135 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 60 | 131 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 72 | 132 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 84 | 119 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 96 | 103 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 108 | 89 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 120 | 87 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 132 | 71 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 144 | 71 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 156 | 64 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 168 | 62 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 180 | 57 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 192 | 41 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 204 | 34 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 216 | 32 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 228 | 20 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 240 | 13 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Clinical Remission at 12-week Intervals | Week 252 | 10 Participants |
Primary
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals
CDAI is a score obtained from composite of eight assessments: number of liquid or soft stools, abdominal pain, general well-being, presence of complications, taking lomotil (diphenoxylate/atropine) or other opiates for diarrhea, presence of an abdominal mass, hematocrit, and percentage deviation from standard weight. A decrease in CDAI over time indicates improvement in disease activity. CDAI scores range from 0 to 600. A higher score indicates worse outcome. A total score of less than 150 corresponds to remission.
Time frame: Day 1 and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240 and 252 of OLE
Population: OLE population included all participants who received at least one dose of study drug in Study GA29145 Part 1 (OLE). Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 108 | 96 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Day 1 | 230 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 12 | 166 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 24 | 165 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 36 | 161 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 48 | 113 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 60 | 137 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 72 | 124 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 84 | 119 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 96 | 88 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 120 | 85 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 132 | 73 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 144 | 62 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 156 | 58 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 168 | 57 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 180 | 53 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 192 | 39 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 204 | 29 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 216 | 32 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 228 | 18 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 240 | 13 Participants |
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals | Week 252 | 12 Participants |
Primary
Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0
Hypersensitivity was reported using the MedDRA anaphylactic reaction standard MedDRA query (SMQ) and Sampson's criteria. 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 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| 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, Grade 3 | 1 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 | 3 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 | 2 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 | 0 Participants |
Primary
Part 1: Number of Participants With Improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 108
SES-CD is an endoscopic score composite of 4 variables (ulcers size, percentage of ulcerated surface, inflamed surface, and presence of narrowing) in up to 5 ileocolonic segments (ileum right, colon, transverse colon, left colon, rectum) and scored on a scale of 0-3, with total score from 0-60. Higher score indicates higher ulcer surface/size in the 4 variables. Endoscopic improvement was defined as ≥50% reduction in SES-CD score compared to baseline.
Time frame: At OLE Week 108
Population: OLE population included all participants who received at least one dose of study drug in Study GA29145 Part 1 (OLE). Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 108 | 147 Participants |
Primary
Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0
AE=untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. AEs were graded 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. If a participant experienced multiple occurrences of AEs at different grades, they were counted in each grade where they had at least one AE of that grade.
Time frame: From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| 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 | 366 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 | Grade 1 Infection Related AEs | 239 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 | Grade 2 Infection Related AEs | 194 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 | Grade 3 Infection Related AEs | 56 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 | Grade 4 Infection Related AEs | 5 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 | Grade 5 Infection Related AEs | 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 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 safety 12-week follow-up in OLE (approximately 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| 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 Reaction, Any Grade | 15 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 Reaction, Grade 1 | 14 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 Reaction, Grade 2 | 1 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 Reaction, 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 Reaction, Grade 4 | 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 Reaction, Grade 5 | 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 6.3 years)
Population: OLE population included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Malignancies | 18 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 6.3 years)
Population: OLE popuation included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Serious Adverse Events (SAEs) | 206 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 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 6.3 years)
Population: OLE popuation included all participants who received at least one dose of study drug in study GA29145 Part 1 (OLE).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 1: Number of Participants With Serious Infection Related AES | 58 Participants |
Primary
Part 2: Number of Participants With Confirmed or Suspected Progressive Multifocal Leukoencephalopathy (PML)
PML was assessed by the PML Subjective Checklist (symptom assessment) and the PML Objective Checklist (neurologic evaluation).
Time frame: From end of safety follow-up in Part 1 or study GA29144 up to maximum of 92 weeks
Population: PML SM population included all participants who entered the PML SM phase. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (OLE): Etrolizumab | Part 2: Number of Participants With Confirmed or Suspected Progressive Multifocal Leukoencephalopathy (PML) | 0 Participants |