Trial Outcomes & Findings for A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors (NCT NCT02136069)

NCT ID: NCT02136069

Last Updated: 2021-12-03

Results Overview

Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Clinical Remission is MCS ≤2 with individual subscores ≤1.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 397 participants
• Primary outcome timeframe: Week 10, Week 54
• Results posted on: 2021-12-03

Participant Flow

Participant milestones

Measure	Etrolizumab + Placebo (IV) Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Overall Study STARTED	199	198
Overall Study COMPLETED	165	170
Overall Study NOT COMPLETED	34	28

Reasons for withdrawal

Measure	Etrolizumab + Placebo (IV) Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Overall Study UC flare-up	1	0
Overall Study Adverse Event	6	8
Overall Study Death	0	1
Overall Study Lack of Efficacy	10	4
Overall Study Lost to Follow-up	1	0
Overall Study Non-Compliance	1	0
Overall Study Physician Decision	5	4
Overall Study Withdrawal by Subject	10	11

Baseline Characteristics

For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.

Baseline characteristics by cohort

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.	Total n=397 Participants Total of all reporting groups
Age, Continuous	40.0 years STANDARD_DEVIATION 15.2 • n=199 Participants	39.5 years STANDARD_DEVIATION 13.4 • n=198 Participants	39.8 years STANDARD_DEVIATION 14.3 • n=397 Participants
Sex: Female, Male Female	81 Participants n=199 Participants	66 Participants n=198 Participants	147 Participants n=397 Participants
Sex: Female, Male Male	118 Participants n=199 Participants	132 Participants n=198 Participants	250 Participants n=397 Participants
Race/Ethnicity, Customized Asian	39 Participants n=199 Participants	30 Participants n=198 Participants	69 Participants n=397 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=199 Participants	0 Participants n=198 Participants	1 Participants n=397 Participants
Race/Ethnicity, Customized White	150 Participants n=199 Participants	158 Participants n=198 Participants	308 Participants n=397 Participants
Race/Ethnicity, Customized Other	9 Participants n=199 Participants	10 Participants n=198 Participants	19 Participants n=397 Participants
Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline MCS ≤9	139 Participants n=199 Participants • For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.	147 Participants n=197 Participants • For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.	286 Participants n=396 Participants • For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.
Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline MCS ≥10	60 Participants n=199 Participants • For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.	50 Participants n=197 Participants • For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.	110 Participants n=396 Participants • For the Infliximab arm, only 197 subjects had MCS categorical scores available for baseline.
Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS Corticosteroids (CS) Alone	59 Participants n=199 Participants	56 Participants n=198 Participants	115 Participants n=397 Participants
Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS Immunosuppressants (IS) Alone	40 Participants n=199 Participants	36 Participants n=198 Participants	76 Participants n=397 Participants
Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS Both CS and IS	25 Participants n=199 Participants	30 Participants n=198 Participants	55 Participants n=397 Participants
Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS None	75 Participants n=199 Participants	76 Participants n=198 Participants	151 Participants n=397 Participants

PRIMARY outcome

Timeframe: Week 10, Week 54

Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

Clinical Remission is MCS ≤2 with individual subscores ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)	18.6 percentage of participants	19.7 percentage of participants

SECONDARY outcome

Timeframe: Week 10

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1	20.6 percentage of participants	32.8 percentage of participants

SECONDARY outcome

Timeframe: Week 54

Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Remission is MCS ≤2 with individual subscores ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS	20.1 percentage of participants	23.7 percentage of participants

SECONDARY outcome

Timeframe: Week 10 and Week 54

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Remission is MCS ≤2 with individual subscores ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS	10.6 percentage of participants	13.1 percentage of participants

SECONDARY outcome

Timeframe: Week 10 and Week 54

Population: Participants that achieved a Clinical Response at Week 10

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Remission is MCS ≤2 with individual subscores ≤1.

Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=98 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=117 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS	37.8 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 10

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS	36.7 percentage of participants	49.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 54

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS	27.1 percentage of participants	32.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 10, Week 54

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS	18.1 percentage of participants	24.7 percentage of participants

SECONDARY outcome

Timeframe: Week 54

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Endoscopic Remission is Endoscopy subscore = 0.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS	17.6 percentage of participants	22.7 percentage of participants

SECONDARY outcome

Timeframe: Week 10

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS	49.2 percentage of participants	59.1 percentage of participants

SECONDARY outcome

Timeframe: Week 10, Week 54

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS	23.1 percentage of participants	29.3 percentage of participants

SECONDARY outcome

Timeframe: Week 54

Population: Participants that were receiving corticosteroids at baseline

MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

Clinical Remission is MCS ≤2 with individual subscores ≤1.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=84 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=86 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS	15.5 percentage of participants	17.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

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

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) Grade 2	72 participants	74 participants
Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) Grade 3	35 participants	23 participants
Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) Grade 1	42 participants	48 participants
Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) Grade 4	5 participants	5 participants
Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) Grade 5	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Adverse Events Leading to Study Drug Discontinuation	29 participants	25 participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

All 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.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 Grade 4	2 participants	1 participants
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 Grade 5	0 participants	0 participants
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 Grade 1	28 participants	27 participants
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 Grade 2	31 participants	29 participants
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 Grade 3	8 participants	4 participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Serious Infection-Related Adverse Events	11 participants	3 participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Malignancies	3 participants	1 participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

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

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 Grade 1	7 participants	5 participants
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 Grade 2	0 participants	2 participants
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 Grade 3	0 participants	0 participants
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 Grade 4	0 participants	0 participants
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 Grade 5	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline until the end of study (up to 66 weeks)

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

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=199 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 Grade 1	0 participants	2 participants
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 Grade 2	0 participants	7 participants
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 Grade 3	0 participants	1 participants
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 Grade 4	0 participants	2 participants
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 Grade 5	0 participants	0 participants

SECONDARY outcome

Timeframe: Weeks 2, 10, 12, 30, and 54

Population: A subset of etrolizumab-treated participants who received at least one dose of study drug and had at least one quantifiable concentration measured post baseline.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=153 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Pharmacokinetics: Etrolizumab Serum Concentration Week 2	7.64 microgram/milliliter Standard Deviation 2.75	—
Pharmacokinetics: Etrolizumab Serum Concentration Week 10	12.0 microgram/milliliter Standard Deviation 4.63	—
Pharmacokinetics: Etrolizumab Serum Concentration Week 12	6.92 microgram/milliliter Standard Deviation 3.18	—
Pharmacokinetics: Etrolizumab Serum Concentration Week 32	13.9 microgram/milliliter Standard Deviation 5.96	—
Pharmacokinetics: Etrolizumab Serum Concentration Week 54	13.2 microgram/milliliter Standard Deviation 5.68	—

SECONDARY outcome

Timeframe: Weeks 10, 30, and 54

Population: Participants that completed the IBDQ Questionnaire at baseline and at the respective Time Points

The IBDQ is used to assess participant's health-related quality of life (QOL). The 32-item questionnaire contains four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale with a higher score indicating better health-related QOL.

IBDQ score is a total score summed up from across all 32 questions on the questionnaire. The score can range from 32-224 and the higher score indicates a better quality of life.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=165 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=156 Participants Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 Week 30	53.5 scores on a scale Standard Deviation 40.8	59.6 scores on a scale Standard Deviation 34.4
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 Week 54	58.2 scores on a scale Standard Deviation 32.9	63.2 scores on a scale Standard Deviation 38.5
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 Week 10	43.2 scores on a scale Standard Deviation 36.6	45.1 scores on a scale Standard Deviation 39.4

SECONDARY outcome

Timeframe: Weeks 0, 4, 10, 12, 30, and 54

Population: A subset of etrolizumab-treated participants with at least one baseline or post-baseline ATA result from at least one sample.

Outcome measures

Measure	Etrolizumab + Placebo (IV) n=196 Participants Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab	69 participants	—

Adverse Events

Etrolizumab + Placebo (IV)

Serious events: 32 serious events

Other events: 94 other events

Deaths: 0 deaths

Infliximab + Placebo (Injection)

Serious events: 20 serious events

Other events: 80 other events

Deaths: 1 deaths

Serious adverse events

Measure	Etrolizumab + Placebo (IV) n=199 participants at risk Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 participants at risk Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Blood and lymphatic system disorders Anaemia	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Eye disorders Retinal vein occlusion	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Abdominal pain	1.0% 2/199 • Number of events 2 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Colitis ulcerative	6.0% 12/199 • Number of events 12 • Baseline until the end of study (up to 66 weeks)	5.6% 11/198 • Number of events 11 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Incarcerated umbilical hernia	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Pancreatitis acute	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Immune system disorders Anaphylactic reaction	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Immune system disorders Drug hypersensitivity	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Immune system disorders Hypersensitivity	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Anal abscess	1.5% 3/199 • Number of events 3 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Appendicitis	1.0% 2/199 • Number of events 2 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Bacteraemia	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Cytomegalovirus colitis	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Lower respiratory tract infection	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Meningitis listeria	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Orchitis	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Pneumonia	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Pyelonephritis	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Sepsis	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Stitch abscess	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Viral upper respiratory tract infection	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Injury, poisoning and procedural complications Incisional hernia	0.50% 1/199 • Number of events 2 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Injury, poisoning and procedural complications Procedural intestinal perforation	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Injury, poisoning and procedural complications Tendon rupture	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Investigations Haemoglobin decreased	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Nervous system disorders Central nervous system vasculitis	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Renal and urinary disorders Haematuria	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Renal and urinary disorders Renal colic	1.0% 2/199 • Number of events 2 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/199 • Baseline until the end of study (up to 66 weeks)	0.51% 1/198 • Number of events 1 • Baseline until the end of study (up to 66 weeks)
Skin and subcutaneous tissue disorders Pyoderma gangrenosum	0.50% 1/199 • Number of events 1 • Baseline until the end of study (up to 66 weeks)	0.00% 0/198 • Baseline until the end of study (up to 66 weeks)

Other adverse events

Measure	Etrolizumab + Placebo (IV) n=199 participants at risk Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Infliximab + Placebo (Injection) n=198 participants at risk Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Gastrointestinal disorders Abdominal pain	5.0% 10/199 • Number of events 11 • Baseline until the end of study (up to 66 weeks)	2.5% 5/198 • Number of events 6 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Colitis ulcerative	22.6% 45/199 • Number of events 47 • Baseline until the end of study (up to 66 weeks)	16.7% 33/198 • Number of events 36 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Diarrhoea	5.5% 11/199 • Number of events 12 • Baseline until the end of study (up to 66 weeks)	2.0% 4/198 • Number of events 4 • Baseline until the end of study (up to 66 weeks)
Gastrointestinal disorders Nausea	5.0% 10/199 • Number of events 10 • Baseline until the end of study (up to 66 weeks)	2.0% 4/198 • Number of events 4 • Baseline until the end of study (up to 66 weeks)
Infections and infestations Nasopharyngitis	11.1% 22/199 • Number of events 30 • Baseline until the end of study (up to 66 weeks)	11.6% 23/198 • Number of events 30 • Baseline until the end of study (up to 66 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	10.6% 21/199 • Number of events 24 • Baseline until the end of study (up to 66 weeks)	7.6% 15/198 • Number of events 16 • Baseline until the end of study (up to 66 weeks)
Nervous system disorders Headache	11.1% 22/199 • Number of events 30 • Baseline until the end of study (up to 66 weeks)	9.6% 19/198 • Number of events 28 • Baseline until the end of study (up to 66 weeks)

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER