Trial Outcomes & Findings for Open-Label Extension and Safety Study for Participants With Crohn's Disease Previously Enrolled in the Etrolizumab Phase III Study GA29144 (NCT NCT02403323)

Last Updated: 2024-12-02

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

790 participants

Primary outcome timeframe

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

Results posted on

2024-12-02

Participant Flow

Participants were enrolled in this study in 33 countries. All participants who enrolled into this study previously took part in study GA29144 (NCT02394028).

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.

Participant milestones

Participant milestones
Measure	Part 1 (OLE): Etrolizumab Only Participants received etrolizumab 105 milligrams (mg), subcutaneously (SC), once every 4 weeks (Q4W) for a maximum of 320 weeks followed by a 12-week safety follow-up.	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.	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.
Part 1: Open Label Extension Period STARTED	431	320	0
Part 1: Open Label Extension Period COMPLETED	5	320	0
Part 1: Open Label Extension Period NOT COMPLETED	426	0	0
Part 2: PML Safety Monitoring Period STARTED	0	320	39
Part 2: PML Safety Monitoring Period COMPLETED	0	112	33
Part 2: PML Safety Monitoring Period NOT COMPLETED	0	208	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1 (OLE): Etrolizumab Only Participants received etrolizumab 105 milligrams (mg), subcutaneously (SC), once every 4 weeks (Q4W) for a maximum of 320 weeks followed by a 12-week safety follow-up.	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.	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.
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 Reason Not Specified	59	0	0
Part 1: Open Label Extension Period Physician Decision	61	0	0
Part 1: Open Label Extension Period Study Terminated By Sponsor	19	0	0
Part 1: Open Label Extension Period Other	1	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 Reason Not Specified	0	6	1
Part 2: PML Safety Monitoring Period Physician Decision	0	7	0
Part 2: PML Safety Monitoring Period Study Terminated By Sponsor	0	167	0
Part 2: PML Safety Monitoring Period Other	0	1	0
Part 2: PML Safety Monitoring Period Withdrawal by Subject	0	12	2

Baseline Characteristics

Open-Label Extension and Safety Study for Participants With Crohn's Disease Previously Enrolled in the Etrolizumab Phase III Study GA29144

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 (OLE): Etrolizumab Only n=431 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.	Part 1 (OLE) to Part 2 (PML SM) n=320 Participants 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.	Part 2 (PML SM) Only n=39 Participants 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.	Total n=790 Participants Total of all reporting groups
Age, Continuous	37.8 years STANDARD_DEVIATION 13.0 • n=5 Participants	39.7 years STANDARD_DEVIATION 13.6 • n=7 Participants	36.8 years STANDARD_DEVIATION 13.0 • n=5 Participants	38.5 years STANDARD_DEVIATION 13.2 • n=4 Participants
Sex: Female, Male Female	199 Participants n=5 Participants	158 Participants n=7 Participants	19 Participants n=5 Participants	376 Participants n=4 Participants
Sex: Female, Male Male	232 Participants n=5 Participants	162 Participants n=7 Participants	20 Participants n=5 Participants	414 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	24 Participants n=7 Participants	3 Participants n=5 Participants	51 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	385 Participants n=5 Participants	280 Participants n=7 Participants	35 Participants n=5 Participants	700 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	22 Participants n=5 Participants	16 Participants n=7 Participants	1 Participants n=5 Participants	39 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Asian	25 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	35 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	27 Participants n=4 Participants
Race/Ethnicity, Customized White	358 Participants n=5 Participants	277 Participants n=7 Participants	33 Participants n=5 Participants	668 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	21 Participants n=5 Participants	14 Participants n=7 Participants	1 Participants n=5 Participants	36 Participants n=4 Participants
Race/Ethnicity, Customized Other	10 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	17 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Day 1	230 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 12	166 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 24	165 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 36	161 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 48	113 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 60	137 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 72	124 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 84	119 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 96	88 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 108	96 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 120	85 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 132	73 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 144	62 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 156	58 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 168	57 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 180	53 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 192	39 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 204	29 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 216	32 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 228	18 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 240	13 Participants
Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Week 252	12 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 12	161 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 36	162 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 48	135 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 84	119 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 96	103 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 108	89 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 120	87 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 132	71 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 144	71 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 156	64 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 168	62 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 180	57 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 192	41 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 204	34 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 216	32 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 228	20 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 252	10 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Day 1	200 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 24	168 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 60	131 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 72	132 Participants
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Week 240	13 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=242 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 108	147 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
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: 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: 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: 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: 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
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

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Serious Adverse Events (SAEs)	206 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
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: 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: 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: 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: 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: 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 outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Incidence Rate of Infection-related Adverse Event	62.74 event per 100 participant-years Interval 58.74 to 66.94

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Serious Infection Related AES	58 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
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: 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: 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: 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: 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
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

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Adverse Events Leading to Etrolizumab Discontinuation	112 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Number of Participants With Malignancies	18 Participants

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 1: Incidence Rate of Malignancies	1.85 events per 100-participant-years Interval 1.22 to 2.7

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=751 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
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: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 Hypersensitivity Reactions, Grade 3	1 Participants
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: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 Hypersensitivity Reactions, Grade 2	0 Participants

PRIMARY outcome

Timeframe: 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.

PML was assessed by the PML Subjective Checklist (symptom assessment) and the PML Objective Checklist (neurologic evaluation).

Outcome measures

Outcome measures
Measure	Part 1 (OLE): Etrolizumab n=359 Participants Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.
Part 2: Number of Participants With Confirmed or Suspected Progressive Multifocal Leukoencephalopathy (PML)	0 Participants

Adverse Events

Part 1 (OLE): Etrolizumab

Serious events: 206 serious events

Other events: 453 other events

Deaths: 3 deaths

Part 2 (PML SM)

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Part 1 (OLE): Etrolizumab n=751 participants at risk Participants received etrolizumab 105 mg, SC, Q4W for a maximum of 320 weeks followed by a 12-week safety follow-up.	Part 2 (PML SM) n=359 participants at risk Participants from Part 1 (OLE) and from the study GA29144 who were not eligible/did not wish to enroll in Part 1 (OLE) and had completed the 12-week safety follow-up period were enrolled in Part 2 (PML SM). Participants were monitored for PML for a maximum of 92-weeks, during which no etrolizumab treatment was administered.
Blood and lymphatic system disorders Anaemia	5.6% 42/751 • Number of events 52 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Gastrointestinal disorders Abdominal pain	10.9% 82/751 • Number of events 109 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.28% 1/359 • Number of events 2 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Gastrointestinal disorders Crohn's disease	23.2% 174/751 • Number of events 229 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.28% 1/359 • Number of events 1 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Gastrointestinal disorders Diarrhoea	7.1% 53/751 • Number of events 68 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Gastrointestinal disorders Nausea	6.9% 52/751 • Number of events 63 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Gastrointestinal disorders Vomiting	5.7% 43/751 • Number of events 52 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Infections and infestations COVID-19	10.7% 80/751 • Number of events 81 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Infections and infestations Nasopharyngitis	10.7% 80/751 • Number of events 136 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Infections and infestations Upper respiratory tract infection	7.7% 58/751 • Number of events 80 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Infections and infestations Urinary tract infection	5.1% 38/751 • Number of events 46 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.28% 1/359 • Number of events 1 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Musculoskeletal and connective tissue disorders Arthralgia	11.6% 87/751 • Number of events 119 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Musculoskeletal and connective tissue disorders Back pain	5.7% 43/751 • Number of events 52 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.
Nervous system disorders Headache	10.1% 76/751 • Number of events 96 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.	0.00% 0/359 • Part 1 (OLE): From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years); Part 2 (PML SM): From end of safety follow-up in Part 1 or in study GA29144 up to a maximum of 92-weeks OLE population included all participants who received at least one dose of open label etrolizumab in Part 1 of the study. PML SM population included all participants who entered the PML SM period. Part 2: PML SM arm includes all participants who entered Part 2 (PML SM) from Part 1 (OLE) or from the parent study GA29144. No treatment was administered in PML SM period, and hence participants entering from Part 1 (OLE) and the parent study have been reported together.

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