A Phase I Study of Etrolizumab Followed by Open-Label Ext... | NCT03478956

ID	Type	Description	Link
2017-003649-10	EudraCT Number

Label	Type	Description	Intervention Names
Etrolizumab Q4W	Experimental	Etrolizumab 1.5 milligrams per kilogram of body weight (mg/kg) was administered by subcutaneous (SC) injection once every 4 weeks (Q4W) for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase.	Drug: Etrolizumab
Etrolizumab Q8W	Experimental	Etrolizumab 3.0 mg/kg was administered by subcutaneous (SC) injection once every 8 weeks (Q8W) for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase.	Drug: Etrolizumab

Name	Type	Description	Arm Group Labels	Other Names
Etrolizumab	Drug	Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.	Etrolizumab Q4W Etrolizumab Q8W

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase	Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.	Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56
Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase	Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.	Arm Etro Q4W: Days 1, 84 and Arm Etro Q8W: Days 1, 56
Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase	Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.	Arm Etro Q4W: Days 56, 84, 88, 98, 112 and Arm Etro Q8W: Day 56, 60, 70, 84, 88, 98, 112
Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase	Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.	Arm Etro Q4W: Days 84, 88, 98, 112, 126, 140, 168 and Arm Etro Q8W: Days 56, 60, 70, 84, 88, 98, 112, 126, 140, 168
Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase	Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age of 4 years to <18 years at the time of signing the Informed Consent Form.
Weight of 13 kilograms (kg) or more
Diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) confirmed by biopsy and established for ≥3 months (i.e., after first diagnosis by a physician according to American College of Gastroenterology [ACG] guidelines) prior to screening
Inadequate response, loss of response or intolerance to prior immunosuppressants and/or corticosteroid treatment and/or anti-tumor necrosis factor (TNF) therapy
For postpubertal females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 24 weeks after the last dose of etrolizumab.
For male patients: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

Pregnant or lactating
Lack of peripheral venous access
Congenital or acquired immune deficiency
Neurological conditions or diseases that may interfere with monitoring for progressive multifocal leukoencephalopathy (PML)
History of demyelinating disease
History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening

Exclusion Criteria Related to Inflammatory Bowel Disease:

Prior extensive colonic resection, subtotal or total colectomy, or planned surgery
Past or present ileostomy or colostomy
Diagnosis of indeterminate colitis
Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
Diagnosis of toxic megacolon within 12 months of initial screening visit
Abdominal abscess
A history or current evidence of colonic mucosal dysplasia
Patients with fixed symptomatic stenosis of the intestine
Patients with history or evidence of adenomatous colonic polyps that have not been removed

Exclusion Criteria Related to Ulcerative Colitis:

Severe extensive colitis per investigator judgment that colectomy is imminent

Exclusion Criteria Related to Crohn's Disease:

Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical judgment of the investigator
Short-bowel syndrome
Evidence of abdominal or perianal abscess
Expected to require surgery to manage CD-related complications during the study

Exclusion Criteria Related to Prior or Concomitant Therapy:

Any prior treatment with anti-integrin agents (including natalizumab, vedolizumab, and efalizumab), ustekinumab, anti-adhesion molecules (e.g., anti-MAdCAM-1), or rituximab
Use of IV steroids within 30 days prior to screening with the exception of a single administration of IV steroid
Use of agents that deplete B or T cells (e.g., alemtuzumab or visilizumab) within 12 months prior to Day 1, with the exception of AZA and 6-MP
Use of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 4 weeks prior to Day 1
Use of other biologics (e.g. anti-TNF) within 8 weeks before dosing (unless drug level is below detectability before completion of the 8-week interval)
Chronic nonsteroidal anti-inflammatory drug (NSAID) use
Patients who are currently using anticoagulants
Apheresis (i.e., Adacolumn apheresis) within 2 weeks prior to Day 1
Received any investigational treatment including investigational vaccines within 12 weeks prior to Day 1 of the study or 5 half-lives of the investigational product, whichever is greater
History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or hypersensitivity to etrolizumab (active drug substance) or any of the excipients (L-histidine, L-arginine, succinic acid, polysorbate 20)

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Hôpital Enfants Reine Fabiola		Brussels		1020	Belgium
Gabinet Lekarski, Bartosz Korczowski

ID	Title	Description
FG000	Etrolizumab Q4W	Etrolizumab 1.5 milligrams per kilogram of body weight (mg/kg) was administered by subcutaneous (SC) injection once every 4 weeks (Q4W) for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 28, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase

Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.

Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their first dose (Day 1 for both arms) and last dose (on Day 56 for Q8W arm and Day 84 for Q4W arm) of study drug.

Posted

Mean

Standard Deviation

micrograms per millilitre (μg/mL)

Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts
Participants	OG00011 OG00112

Title

Denominators

Categories

After First Dose (Day 1)

- ParticipantsOG00010
- ParticipantsOG00112

Title	Measurements
	OG0007.73± 2.18

Primary

Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase

Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.

Posted

Mean

Standard Deviation

Day

Arm Etro Q4W: Days 1, 84 and Arm Etro Q8W: Days 1, 56

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts

Primary

Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase

Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.

Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their last dose of study drug (on Day 56 for Q8W arm and Day 84 for Q4W arm).

Posted

Mean

Standard Deviation

Day*μg/mL

Arm Etro Q4W: Days 56, 84, 88, 98, 112 and Arm Etro Q8W: Day 56, 60, 70, 84, 88, 98, 112

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts

Primary

Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase

Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.

Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants who had received their last dose of study drug (on Day 56 for Q8W arm and Day 84 for Q4W arm).

Posted

Mean

Standard Deviation

Day

Arm Etro Q4W: Days 84, 88, 98, 112, 126, 140, 168 and Arm Etro Q8W: Days 56, 60, 70, 84, 88, 98, 112, 126, 140, 168

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts

Primary

Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase

Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method.

Pharmacokinetics (PK) Evaluable Population: all participants who received at least one dose of study drug and had evaluable PK data. This analysis included data from participants at the end of each dosing interval (on Days 28, 56, 84, and 112 for Q4W arm and Days 56 and 112 for Q8W arm).

Posted

Mean

Standard Deviation

micrograms per millilitre (μg/mL)

Arm Etro Q4W: Predose on Days 28, 56, 84, 112 and Arm Etro Q8W: Predose on Days 56, 112

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts

Primary

Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase

Target engagement of etrolizumab was assessed via measurement of Beta7 receptor occupancy on Beta7 receptor-expressing gut homing lymphocyte subsets in peripheral blood, including CD3, CD4, and CD8 T cells and CD19 B cells, using qualified flow cytometry methods. A decrease to 0% of baseline (BL) in median absolute cell counts of Beta7 receptor-expressing T and B cell subsets with unoccupied Beta7 receptors following etrolizumab treatment indicated maximal receptor occupancy by etrolizumab.

Pharmacodynamics (PD) Evaluable Population: all participants who received at least one dose of study treatment and had evaluable PD data.

Posted

Median

Standard Deviation

Percentage of BL Unoccupied Beta7 Cells

Predose (dosing days only) at Baseline (Day 1) and on Days 4, 56, 84, 98, and 112 (Treatment Period), and Days 126, 140, and 168 (Follow-Up Period)

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Secondary

Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase

All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.

Safety Population: all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Secondary

Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase

Serious infection-related AEs were assessed using NCI-CTCAE v4.0.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts
Participants

Secondary

Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase

Hypersensitivity reactions were assessed using NCI-CTCAE v4.0.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts
Participants

Secondary

Number of Participants With Malignancies During the Randomized Treatment Phase

Malignancies were assessed using NCI-CTCAE v4.0.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).

Units	Counts
Participants	OG000

Secondary

Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase

Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative).

ADA Evaluable Population: all participants who received at least one dose of study treatment and had at least one baseline or post-baseline ADA result from at least one sample.

Posted

Count of Participants

Participants

Predose (dosing days only) on Days 1, 28, 84, 112, and 168 (up to the end of the randomized treatment phase at Week 24)

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
OG001	Etrolizumab Q8W

Secondary

Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0

Safety Population: all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks

ID	Title	Description
OG000	OLE: Etrolizumab 1.5 mg Q4W	Participants from Etrolizumab Q4W and Etrolizumab Q8W who completed the randomized treatment period, were given the option to participate in the OLE period. All participants who chose to enter the OLE period were administered etrolizumab 1.5 mg/kg SC Q4W for a maximum of 183 weeks. Post treatment discontinuation participants entered a 12-week safety follow up.

Secondary

Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events

Serious infection-related AEs were assessed using NCI-CTCAE v4.0.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

ID	Title	Description
OG000	OLE: Etrolizumab 1.5 mg Q4W	Participants from Etrolizumab Q4W and Etrolizumab Q8W who completed the randomized treatment period, were given the option to participate in the OLE period. All participants who chose to enter the OLE period were administered etrolizumab 1.5 mg/kg SC Q4W for a maximum of 183 weeks. Post treatment discontinuation participants entered a 12-week safety follow up.
OG001	PML Safety Monitoring	After the randomized treatment period (if participants did not enter the OLE period) or after the OLE period, participants who chose to continue in PML safety surveillance phase were monitored for PML for approximately 92 weeks. Participants who chose to enter PML surveillance phase were only followed up for PML and did not receive any study treatment.

Secondary

Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions

Hypersensitivity reactions were assessed using NCI-CTCAE v4.0.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

ID	Title	Description
OG000	OLE: Etrolizumab 1.5 mg Q4W	Participants from Etrolizumab Q4W and Etrolizumab Q8W who completed the randomized treatment period, were given the option to participate in the OLE period. All participants who chose to enter the OLE period were administered etrolizumab 1.5 mg/kg SC Q4W for a maximum of 183 weeks. Post treatment discontinuation participants entered a 12-week safety follow up.
OG001	PML Safety Monitoring	After the randomized treatment period (if participants did not enter the OLE period) or after the OLE period, participants who chose to continue in PML safety surveillance phase were monitored for PML for approximately 92 weeks. Participants who chose to enter PML surveillance phase were only followed up for PML and did not receive any study treatment.

Secondary

Long-Term Safety of Etrolizumab: Number of Participants With Malignancies

Malignancies were assessed using NCI-CTCAE v4.0.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

ID	Title	Description
OG000	OLE: Etrolizumab 1.5 mg Q4W	Participants from Etrolizumab Q4W and Etrolizumab Q8W who completed the randomized treatment period, were given the option to participate in the OLE period. All participants who chose to enter the OLE period were administered etrolizumab 1.5 mg/kg SC Q4W for a maximum of 183 weeks. Post treatment discontinuation participants entered a 12-week safety follow up.
OG001	PML Safety Monitoring	After the randomized treatment period (if participants did not enter the OLE period) or after the OLE period, participants who chose to continue in PML safety surveillance phase were monitored for PML for approximately 92 weeks. Participants who chose to enter PML surveillance phase were only followed up for PML and did not receive any study treatment.

Secondary

Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline

ADA Evaluable Population: all participants who received at least one dose of study treatment and had at least one baseline or post-baseline ADA result from at least one sample.

Posted

Count of Participants

Participants

Predose (dosing days only) at Baseline (Day 1), Days 28, 84, and 112, Weeks 24, 36, 72, and 120, and every 12 weeks thereafter for up to 4.25 years

ID	Title	Description
OG000	Etrolizumab Q4W	Etrolizumab 1.5 milligrams mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up). Thereafter, participants were given the option to participate in the OLE period to receive etrolizumab 1.5 mg/kg SC Q4W for maximum of 183 weeks. After the randomized treatment period or OLE period participants who chose to enroll in the PML safety surveillance phase were monitored for PML for approximately 92 weeks.

Secondary

Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase

The safety surveillance PML-monitoring phase (no etrolizumab treatment) consisted of telephone calls approximately every 6 months with administration of the protocol's PML Subjective Checklist. If there were any signs or symptoms suggestive of PML identified on this subjective checklist during the telephone call, the participant was asked to come into the clinic for a neurologic examination. The protocol's PML Algorithm was followed for any suspected case of PML, and any confirmed case of PML would be reported as a serious adverse event.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

PML Period: After completion of safety follow up in Randomized Treatment period or after completion of safety follow up after OLE treatment, up to approximately 92 weeks

ID	Title	Description
OG000	PML Safety Monitoring	After the randomized treatment period (if participants did not enter the OLE period) or after the OLE period, participants who chose to continue in PML safety surveillance phase were monitored for PML for approximately 92 weeks. Participants who chose to enter PML surveillance phase were only followed up for PML and did not receive any study treatment.

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG0030 events0 affected13 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0022 events2 affected21 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0022 events2 affected21 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Anxiety disorder	Psychiatric disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Sinusitis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Idiopathic intracranial hypertension	Nervous system disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Drug abuse	Psychiatric disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Intentional self-injury	Psychiatric disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Balanoposthitis	Reproductive system and breast disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 26.0	Systematic Assessment	EG0003 events3 affected12 at risk EG0011 events1 affected12 at risk EG0025 events4 affected21 at risk EG0030 events0 affected13 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0003 events3 affected12 at risk EG0014 events2 affected12 at risk EG00212 events6 affected21 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0025 events4 affected21 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events1 affected12 at risk EG0023 events2 affected21 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0002 events2 affected12 at risk EG0010 events0 affected12 at risk EG00213 events7 affected21 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected12 at risk EG0020 events0 affected21 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0002 events2 affected12 at risk EG0012 events2 affected12 at risk EG0029 events5 affected21 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0002 events2 affected12 at risk EG0012 events2 affected12 at risk EG0023 events2 affected21 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0021 events1 affected21 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0023 events3 affected21 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected12 at risk EG0020 events0 affected21 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Peripheral swelling	General disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Pyrexia	General disorders	MedDRA version 26.0	Systematic Assessment	EG0007 events4 affected12 at risk EG0010 events0 affected12 at risk EG0026 events6 affected21 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events1 affected12 at risk EG0025 events2 affected21 at risk EG003
Folliculitis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0020 events0 affected21 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0025 events3 affected21 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0027 events4 affected21 at risk EG003
Respiratory tract infection viral	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0002 events2 affected12 at risk EG0010 events0 affected12 at risk EG00216 events8 affected21 at risk EG003
Varicella	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0021 events1 affected21 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected12 at risk EG0021 events1 affected21 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Weight decreased	Investigations	MedDRA version 26.0	Systematic Assessment	EG0002 events2 affected12 at risk EG0012 events2 affected12 at risk EG0022 events1 affected21 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0020 events0 affected21 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0021 events1 affected21 at risk EG003
Vitamin B12 deficiency	Metabolism and nutrition disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0020 events0 affected21 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0012 events1 affected12 at risk EG0023 events3 affected21 at risk EG003
Headache	Nervous system disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0014 events3 affected12 at risk EG0028 events5 affected21 at risk EG003
Syncope	Nervous system disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Leukocyturia	Renal and urinary disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Amenorrhoea	Reproductive system and breast disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0021 events1 affected21 at risk EG003
Polymenorrhoea	Reproductive system and breast disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0020 events0 affected21 at risk EG003
Catarrh	Respiratory, thoracic and mediastinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0020 events0 affected21 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0022 events1 affected21 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0024 events2 affected21 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0020 events0 affected21 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0022 events2 affected21 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA version 26.0	Systematic Assessment	EG0002 events1 affected12 at risk EG0011 events1 affected12 at risk EG0022 events2 affected21 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected12 at risk EG0021 events1 affected21 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA version 26.0	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Chest pain	General disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0024 events3 affected21 at risk EG003
COVID-19	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0024 events4 affected21 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Herpes zoster	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Oral herpes	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Pharyngitis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0025 events5 affected21 at risk EG003
Rhinitis	Infections and infestations	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0024 events4 affected21 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0022 events2 affected21 at risk EG003
Vaccination site reaction	General disorders	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA version 26.0	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected12 at risk EG0021 events1 affected21 at risk EG003

ID	Term
D003093	Colitis, Ulcerative
D003424	Crohn Disease

ID	Term
D003092	Colitis
D005759	Gastroenteritis
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D015212	Inflammatory Bowel Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases

ID	Title	Description
BG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
BG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Etrolizumab Q4W	Etrolizumab 1.5 mg/kg was administered by SC injection Q4W for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).	12	2	12	8	12
EG001	Etrolizumab Q8W	Etrolizumab 3.0 mg/kg was administered by SC injection Q8W for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment plus 8-week safety follow-up).	12	2	12	9	12
EG002	OLE: Etrolizumab 1.5 mg/kg Q4W	Participants from Etrolizumab Q4W and Etrolizumab Q8W who completed the randomized treatment period, were given the option to participate in the OLE period. All participants who chose to enter the OLE period were administered etrolizumab 1.5 mg/kg SC Q4W for a maximum of 183 weeks. Post treatment discontinuation patients entered a 12-week safety follow up.	21	6	21	20	21
EG003	PML Safety Monitoring	After the randomized treatment period (if participants did not enter the OLE period) or after the OLE period, participants who chose to continue in PML safety surveillance phase were monitored for PML for approximately 92 weeks. Participants who chose to enter PML surveillance phase were only followed up for PML and did not receive any study treatment.	13	0	13	4	13