Symptoms and General Pathology

All Conditions

Digestive System Diseases

Ulcer

Necrosis

Colitis

Colitis, Ulcerative

Gastroenteritis

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Inflammatory Bowel Diseases

Anti-Inflammatory Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Gastrointestinal Agents

Tumor Necrosis Factor Inhibitors

Infliximab

Etrolizumab

Immunologic Factors

Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.

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.

105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.

5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.

Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.

Placebo (IV)

Administered by SC injection Q4W until Week 52

Placebo (Injection)

Clinical Trials

This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous \[IV\] infusion at Weeks 0, 2, and 6, then once every 8 weeks \[Q8W\]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.

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

Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study to Evaluate the Efficacy and Safety of Etrolizumab Compared With Infliximab in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Hoffmann-La Roche

Etrolizumab + Placebo (IV)

Infliximab + Placebo (Injection)

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Race/Ethnicity, Customized

MCS ≤9

MCS ≥10

Measure Description: Participants were stratified by concomitant treatment with corticosteroids (yes/no) at randomization, concomitant treatment with immunosuppressants (yes/no) at randomization, and disease activity measured during screening (MCS ≤9/MCS ≥10). The MCS ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease.

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

Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline

Corticosteroids (CS) Alone

Immunosuppressants (IS) Alone

Both CS and IS

None

Participants were stratified by concomitant treatment with corticosteroids (yes/no) at randomization, concomitant treatment with immunosuppressants (yes/no) at randomization, and disease activity measured during screening (MCS ≤9/MCS ≥10).

Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS

Medical Communications

Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)

Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1

Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS

Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS

Participants that achieved a Clinical Response at Week 10

Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS

Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS

Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS

Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS

Participants that were receiving corticosteroids at baseline

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

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

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)

Number of Participants With Adverse Events Leading to Study Drug Discontinuation

Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0

Number of Participants With Serious Infection-Related Adverse Events

Number of Participants With Malignancies

Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0

Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0

Week 2

Week 10

Week 12

Week 32

Week 54

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.

Pharmacokinetics: Etrolizumab Serum Concentration

Week 30

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

Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54

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

Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab

Overall Study

Adalimumab

Participants will receive placebo matching to etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8.

Participants will receive adalimumab up to Week 8 and placebo matching to etrolizumab up to Week 12.

Participants will receive etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8.

Adalimumab 160 milligrams (mg) will be administered subcutaneously (SC) at Week 0; 80 mg SC at Week 2; 40 mg SC at Weeks 4, 6, and 8.

Placebo matching to adalimumab will be administered SC at Weeks 0, 2, 4, 6, and 8.

Adalimumab Placebo

Etrolizumab 105 mg will be administered SC every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).

Placebo matching to etrolizumab will be administered SC once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).

Etrolizumab Placebo

This Phase III, double-blind, placebo and active-comparator controlled, multicenter study will investigate the efficacy and safety of etrolizumab in induction of remission in participants with moderately to severely active ulcerative colitis (UC) who are naÏve to tumor necrosis factor (TNF) inhibitors and refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment. In addition to this study, a second Phase III trial with identical study design (GA28949; NCT02171429) was independently conducted.

A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors

Phase III, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy (Induction of Remission) and Safety of Etrolizumab Compared With Adalimumab and Placebo in Patients With Moderate to Severe Ulcerative Colitis Who Are Naive to TNF Inhibitors

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Clinical Response was defined as: MCS ≥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. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9 or ≥10); the CMH test adjusted the differences in response rates and associated 95% CIs for the stratification factors.

Improvement in endoscopic appearance of the mucosa was defined as a Mayo Clinic Score (MCS) endoscopy subscore ≤1. Blinded gastroenterologists experienced in inflammatory bowel disease performed central reading of endoscopies at an independent review facility. The rectum, sigmoid, and descending colon segments were assessed and each segment was assigned a score of 0 to 3, with higher scores indicating more severe disease. At baseline all segments were reviewed and the worst score from the three segments was recorded as the endoscopy subscore. Post-baseline the endoscopy score was the worst score of all segments that had been assessed at baseline, if the baseline endoscopy score had a sigmoid colon score ≤1. If at baseline the sigmoid colon score was ≥2, the post-baseline endoscopy score was the sigmoid colon score value. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment.

Endoscopic remission was defined as a Mayo Clinic Score (MCS) endoscopy subscore of 0. Blinded gastroenterologists experienced in inflammatory bowel disease performed central reading of endoscopies at an independent review facility. The rectum, sigmoid, and descending colon segments were assessed and each segment was assigned a score of 0 to 3, with higher scores indicating more severe disease. At baseline all segments were reviewed and the worst score from the three segments was recorded as the endoscopy subscore. Post-baseline the endoscopy score was the worst score of all segments that had been assessed at baseline, if the baseline endoscopy score had a sigmoid colon score ≤1. If at baseline the sigmoid colon score was ≥2, the post-baseline endoscopy score was the sigmoid colon score value. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment.

Histologic remission is defined by the resolution of neutrophilic inflammation (e.g., absence of neutrophils in the crypts and lamina propria), defined by a Nancy Histological Index (NHI) score of ≤1. The NHI score ranges from 0 to 4, with the following definitions for each grade: 0 is no histologically significant disease; 1 is chronic inflammatory infiltrate with no acute inflammatory infiltrate; and 2, 3, and 4 are mildly, moderately, and severely active disease, respectively. A small pool of central readers who were blinded to both treatment arm and timepoint performed the histologic scoring. The same reader scored all slides for a given participant based on biopsies from the most inflamed region of the sigmoid colon. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received rescue therapy prior to assessment. The Cochran-Mantel-Haenszel test adjusted the difference in remission rates and 95% CI for the stratification factors.

Rectal bleeding data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = no blood in the stool; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed. The Mayo Clinic Score (MCS) rectal bleeding subscore was calculated as the worst value of three days of daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline rectal bleeding (RB) subscore.

Stool frequency data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = normal number of stools; 1 = 1 to 2 more stools than normal; 2 = 3 to 4 more stools than normal; 3 = 5 or more stools than normal. The Mayo Clinic Score (MCS) stool frequency subscore was calculated as the average of three days daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline stool frequency (SF) subscore.

The UC-PRO/SS questionnaire was collected in the e-diary and completed by participants for at least 9 to 12 consecutive days prior to a study visit. The bowel movement domain score ranges from 0 to 27, with a higher score indicating a worse disease state. The most recent 7 daily scores available (not including the visit) were selected for the calculation of the visit score. For each item in the questionnaire, a score was calculated for a visit by taking the average of the selected daily scores. The domain score for a visit was calculated as the sum of the averaged items for each question. A Mixed Model for Repeated Measures (MMRM) analysis of the data included the fixed categorical effects of treatment, visit, study stratification factors, and treatment-by-visit interaction, and the continuous covariates of the baseline UC-PRO/SS domain and baseline UC-PRO/SS domain-by-visit interaction. An unstructured covariance matrix was used to model the within-patient errors within the MMRM.

The UC-PRO/SS questionnaire was collected in the e-diary and completed by participants for at least 9 to 12 consecutive days prior to a study visit. The functional symptoms domain score ranges from 0 to 12, with a higher score indicating a worse disease state. The most recent 7 daily scores available (not including the visit) were selected for the calculation of the visit score. For each item in the questionnaire, a score was calculated for a visit by taking the average of the selected daily scores. The domain score for a visit was calculated as the sum of the averaged items for each question. A Mixed Model for Repeated Measures (MMRM) analysis of the data included the fixed categorical effects of treatment, visit, study stratification factors, and treatment-by-visit interaction, and the continuous covariates of the baseline UC-PRO/SS domain and baseline UC-PRO/SS domain-by-visit interaction. An unstructured covariance matrix was used to model the within-patient errors in the MMRM.

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Clinical remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the differences in remission rates and associated 95% confidence intervals for the stratification factors.

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 or 14 assessments were missing or the participant received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the differences in remission rates and associated 95% confidence intervals for the stratification factors.

The IBDQ is a 32-item questionnaire containing four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). An overall total IBDQ score was computed by summing the individual 32-item scores. The range for the IBDQ total score is 32 to 224, with higher scores denoting better health-related quality of life. The unadjusted mean and standard deviation for each study arm are reported. The change from baseline in the IBDQ score was analyzed using an ANCOVA model taking the stratification factors used at randomization into account (concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening \[MCS ≤9/MCS ≥10\]), and the baseline IBDQ score used as a covariate.

Serum concentrations of etrolizumab were evaluated at the primary endpoint visit (Week 10) and the secondary endpoint visit (Week 14). Both time points were two weeks after the most recent dose.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation in which a patient is administered a pharmaceutical product, regardless of causal attribution. The investigator independently assessed the severity and seriousness of each recorded AE. The AE severity grading scale for the NCI CTCAE v4.0 was used for assessing severity; any AE not specifically listed was rated according to the following grading scale from 1 to 5: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death. AEs of special interest included: elevated AST/ALT in combination with either elevated bilirubin or clinical jaundice; suspected transmission of infectious agent by the study drug; anaphylactic, anaphylactoid and systemic hypersensitivity reactions; and neurological signs, symptoms, and AEs that may suggest possible progressive multifocal leukoencephalopathy (PML).

Laboratory tests for hematology parameters were performed and values were compared with the Roche marked reference range. A marked abnormality was defined as a test result that was outside of the Roche marked reference range (labelled as 'High' or 'Low') and represented a clinically significant change from baseline. Not every laboratory abnormality qualified as an adverse event. A laboratory test result must have been reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment or a medical intervention; or was clinically significant in the investigator's judgment. The results are presented as a shift from the baseline status to the Week 10 status. Baseline was defined as the last available assessment prior to first receipt of study drug. The 'missing' status only included participants with missing post-baseline values given they had a result at baseline. Abs = absolute count; Ery. = erythrocyte

Laboratory tests for chemistry parameters were performed and values were compared with the Roche marked reference range. A marked abnormality was defined as a test result that was outside of the Roche marked reference range (labelled as 'High' or 'Low') and represented a clinically significant change from baseline. Not every laboratory abnormality qualified as an adverse event. A laboratory test result must have been reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment or a medical intervention; or was clinically significant in the investigator's judgment. The results are presented as a shift from the baseline status to the Week 10 status. Baseline was defined as the last available assessment prior to first receipt of study drug. The 'missing' status only included participants with missing post-baseline values given they had a result at baseline.

Anti-drug antibody (ADA) serum samples were collected from participants and analyzed using validated assays. Participants were considered to be ADA positive post-baseline if they were ADA negative or had missing data at baseline, but developed an ADA response following etrolizumab drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were ADA negative or had missing data at baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected).

The adverse events reported here are those that occurred only in participants enrolled in study GA28948 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28949, please refer to its study record, NCT02171429.

The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).

Placebo

The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive adalimumab subcutaneously (SC) Q2W up to Week 8 (160 mg at Week 0 \[Day 1\], 80 mg at Week 2, 40 mg at Weeks 4, 6, and 8) and placebo matching to etrolizumab SC Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).

The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).

GA28948 Population

GA28948 & GA28949 Pooled Population

Baseline characteristics are presented for two populations: all 358 participants enrolled in this study, GA28948 (NCT02163759); and a total pooled population of 716 participants, which consists of all 358 participants from this study (GA28948) plus all 358 participants enrolled in a second study of identical design, GA28949 (NCT02171429).

Ethnicity (NIH/OMB)

Disease Location

Participants were stratified by concomitant treatment with corticosteroids (yes/no) at randomization, concomitant treatment with immunosuppressants (yes/no) at randomization, and disease activity measured during screening (MCS ≤9/MCS ≥10). The MCS ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease.

Histologic disease activity was measured using the Nancy Histological Index (NHI) score, ranging from 0 to 4, with the following definitions for each grade: 0 is no histologically significant disease; 1 is chronic inflammatory infiltrate with no acute inflammatory infiltrate; and 2, 3, and 4 are mildly, moderately, and severely active disease, respectively.

Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline

The overall number of baseline participants (716) represents the total number enrolled (358) in this study, GA28948 (NCT02163759), plus the total number enrolled (358) in a second study of identical design, GA28949 (NCT02171429). Some of the pre-specified secondary outcome measure comparisons were planned to be evaluated by pooling data from both studies; all etrolizumab versus adalimumab comparisons and one family of etrolizumab versus placebo comparisons were evaluated on pooled data.

The null hypothesis (H0): the percentage of participants achieving remission at Week 10 was the same in both the placebo and etrolizumab arms. The alternative hypothesis (H1): the percentage of participants achieving remission at Week 10 was not the same in the placebo and etrolizumab arms.

GA28948 Population, Modified Intent-to-Treat: including all randomized participants in study GA28948 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.

Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28948 Population

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. Please refer to the statistical analysis plan for details. This comparison was not considered a key secondary outcome measure and was not part of the multiple testing procedure for statistical significance.

Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 Population

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. This comparison was part of Family 3 of the testing procedure; please refer to the statistical analysis plan for details.

GA28948 \& GA28949 Pooled Population, Modified Intent-to-Treat: including all randomized participants in studies GA28948 \& GA28949 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.

Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. This comparison was part of Family 1 of the testing procedure; please refer to the statistical analysis plan for details.

Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28948 Population

Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. This comparison was part of Family 2 of the testing procedure; please refer to the statistical analysis plan for details.

Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. This comparison was part of Family 5 of the testing procedure; please refer to the statistical analysis plan for details.

Percentage of Participants in Endoscopic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population

GA28948 Histology-Evaluable Population: included all randomized participants in study GA28948 who received at least one dose of study drug and had documented neutrophilic inflammation (i.e., NHI \>1) at baseline. This excludes participants who had no baseline histology assessment or had no indication of neutrophilic inflammation at baseline.

Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28948 Population

GA28948 \& GA28949 Pooled, Histology-Evaluable Population: included all randomized participants in studies GA28948 \& GA28949 who received at least one dose of study drug and had documented neutrophilic inflammation (i.e., NHI \>1) at baseline. This excludes participants who had no baseline histology assessment or had no indication of neutrophilic inflammation at baseline.

Percentage of Participants With Histologic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the Nancy Histological Index, GA28948 & GA28949 Pooled Population

Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28948 Population

Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population

Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28948 Population

Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population

GA28948 Population, Modified Intent-to-Treat: including all randomized participants in study GA28948 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization. The analysis only included participants with non-missing results at baseline and at least one post-baseline timepoint.

Change From Baseline in Ulcerative Colitis (UC) Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS), GA28948 Population

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. This comparison was part of Family 4 of the testing procedure; please refer to the statistical analysis plan for details.

Primary and secondary outcome measures were evaluated for statistical significance in a hierarchical manner with a component-wise multistage gatekeeping procedure. This comparison was part of Family 6 of the testing procedure; please refer to the statistical analysis plan for details.

GA28948 \& GA28949 Pooled Population, Modified Intent-to-Treat: including all randomized participants in studies GA28948 \& GA28949 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization. The analysis only included participants with non-missing results at baseline and at least one post-baseline timepoint.

Change From Baseline in Ulcerative Colitis Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population

Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 Population

Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population

Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28948 Population

Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28948 Population

Change From Baseline in Health-Related Quality of Life at Week 10, as Assessed by the Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score, GA28948 Population

Week 14

GA28948 Pharmacokinetics Evaluable Population: includes participants in study GA28948 who had received at least one dose of study drug and had at least one quantifiable concentration measured post-baseline. Only participants who were treated with etrolizumab were included in this analysis.

Pharmacokinetics of Etrolizumab: Serum Concentration, GA28948 Population

Any Adverse Event (AE)

AE with Fatal Outcome

Serious AE

AE Leading to Study Treatment Discontinuation

AE Leading to Dose Interruption

Related AE

AE by Worst Severity, Grade 1

AE by Worst Severity, Grade 2

AE by Worst Severity, Grade 3

AE by Worst Severity, Grade 4

GA28948 Safety Population: includes all participants in study GA28948 who received at least one dose of study drug, with participants grouped according to the treatment received.

Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28948 Population

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT02136069	Ulcerative Coli...	Etrolizumab Infliximab Placebo (IV) Placebo (Inject...	18 Years - 80 Years	Hoffmann-La Roche
A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors	NCT02163759	Ulcerative Coli...	Adalimumab Adalimumab Plac... Etrolizumab Etrolizumab Pla...	18 Years - 80 Years	Hoffmann-La Roche
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	NCT02136069	Ulcerative Coli...	Etrolizumab Infliximab Placebo (IV) Placebo (Inject...	18 Years - 80 Years	Hoffmann-La Roche
A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors	NCT02171429	Ulcerative Coli...	Adalimumab Adalimumab Plac... Etrolizumab Etrolizumab Pla...	18 Years - 80 Years	Hoffmann-La Roche
A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors	NCT02171429	Ulcerative Coli...	Adalimumab Adalimumab Plac... Etrolizumab Etrolizumab Pla...	18 Years - 80 Years	Hoffmann-La Roche
A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors	NCT02165215	Colitis, Ulcera...	Etrolizumab Placebo	18 Years - 80 Years	Hoffmann-La Roche
A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors	NCT02163759	Ulcerative Coli...	Adalimumab Adalimumab Plac... Etrolizumab Etrolizumab Pla...	18 Years - 80 Years	Hoffmann-La Roche

Spots Global Cancer Trial Database for etrolizumab

Every month we try and update this database with for etrolizumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for etrolizumab

Every month we try and update this database with for etrolizumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for etrolizumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.