Ulcerative Colitis
Conditions
Brief summary
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.
Interventions
DRUGAdalimumab
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.
OTHERAdalimumab Placebo
Placebo matching to adalimumab will be administered SC at Weeks 0, 2, 4, 6, and 8.
DRUGEtrolizumab
Etrolizumab 105 mg will be administered SC every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).
OTHEREtrolizumab Placebo
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 \[clinical remitters only\]).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ulcerative colitis (UC) established at least 3 months prior to randomization (Day 1) * Moderately to severely active UC as determined by the MCS * Naive to treatment with TNF inhibitor therapy * An inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment * Background UC therapy may include oral 5-aminosalisylate (5-ASA), budesonide, oral corticosteroids, probiotics, azathioprine (AZA), 6-mercaptopurine (6MP), or methotrexate (MTX) if doses have been stable for: * AZA, 6-MP, MTX: 8 weeks immediately prior to randomization * 5-ASA: 4 weeks immediately prior to randomization * Corticosteroids: 4 weeks immediately prior to randomization; if corticosteroids are being tapered, dose has to be stable for at least 2 weeks prior to randomization * Use of highly effective contraception method as defined by the protocol * Have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28948 Population | Week 10 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 Population | Week 10 | 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. |
| Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population | Week 10 | 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. |
| Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28948 Population | Week 10 | 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. |
| Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population | Week 10 | 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. |
| Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | Week 10 | 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. |
| 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 | Week 10 | 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. |
| Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | Week 10 | 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. |
| 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 | Week 10 | 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. |
| Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28948 Population | Week 10 | 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. |
| 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 | Week 10 | 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. |
| Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28948 Population | Baseline, Week 6 | 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. |
| Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population | Baseline, Week 6 | 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. |
| Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28948 Population | Baseline, Week 6 | 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. |
| Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population | Baseline, Week 6 | 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. |
| 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 | Baseline, Week 10 | 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. |
| 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 | Baseline, Week 10 | 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. |
| Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 Population | Baseline, Week 10 | 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. |
| Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population | Baseline, Week 10 | 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. |
| Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28948 Population | Week 10 | 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. |
| Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28948 Population | Weeks 10 and 14 | 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. |
| 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 | Baseline, Week 10 | 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. |
| Pharmacokinetics of Etrolizumab: Serum Concentration, GA28948 Population | Weeks 10 and 14 | 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. |
| 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 | From Baseline until the end of study (up to 26 weeks) | 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). |
| Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | From Baseline up to Week 10 | 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 |
| Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | From Baseline up to Week 10 | 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. |
| Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Pre-dose (0 hour) on Day 1 and Week 4, Week 10, Week 14, and early termination/end of safety follow-up (up to 26 weeks) | 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). |
Countries
Argentina, Australia, Brazil, Bulgaria, Estonia, France, Hong Kong, Mexico, Poland, Russia, Serbia, Slovakia, Ukraine, United States
Participant flow
Pre-assignment details
Participants who were on concomitant background therapy were allowed to continue receiving stable baseline doses of the following non-investigational medicinal products during the study: oral 5-aminosalicylic acid; azathioprine; 6-mercaptopurine; methotrexate; corticosteroids up to 30 mg/day of prednisone (or equivalent); and/or budesonide up to 9 mg/day.
Participants by arm
| Arm | Count |
|---|---|
| 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 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). | 144 |
| Adalimumab 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 \[clinical remitters only\]). | 285 |
| Etrolizumab 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). | 287 |
| Total | 716 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Adalimumab | Etrolizumab |
|---|---|---|---|---|
| Age, Continuous GA28948 & GA28949 Pooled Population | 40.4 Years STANDARD_DEVIATION 13.4 | 39.4 Years STANDARD_DEVIATION 12.9 | 40.8 Years STANDARD_DEVIATION 13.2 | 40.6 Years STANDARD_DEVIATION 13.9 |
| Age, Continuous GA28948 Population | 40.5 Years STANDARD_DEVIATION 13.5 | 38.4 Years STANDARD_DEVIATION 13.3 | 42.0 Years STANDARD_DEVIATION 13.8 | 40.1 Years STANDARD_DEVIATION 13.4 |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 & GA28949 Pooled Population Both CS and IS | 88 Participants | 16 Participants | 35 Participants | 37 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 & GA28949 Pooled Population Corticosteroids (CS) Alone | 226 Participants | 48 Participants | 88 Participants | 90 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 & GA28949 Pooled Population Immunosuppressants (IS) Alone | 147 Participants | 29 Participants | 58 Participants | 60 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 & GA28949 Pooled Population None | 255 Participants | 51 Participants | 104 Participants | 100 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 Population Both CS and IS | 40 Participants | 8 Participants | 15 Participants | 17 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 Population Corticosteroids (CS) Alone | 121 Participants | 25 Participants | 46 Participants | 50 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 Population Immunosuppressants (IS) Alone | 77 Participants | 15 Participants | 30 Participants | 32 Participants |
| Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS GA28948 Population None | 120 Participants | 24 Participants | 51 Participants | 45 Participants |
| Disease Location GA28948 & GA28949 Pooled Population Extensive Colitis | 86 Participants | 17 Participants | 36 Participants | 33 Participants |
| Disease Location GA28948 & GA28949 Pooled Population Left-Sided Colitis | 437 Participants | 92 Participants | 170 Participants | 175 Participants |
| Disease Location GA28948 & GA28949 Pooled Population Pancolitis | 193 Participants | 35 Participants | 79 Participants | 79 Participants |
| Disease Location GA28948 Population Extensive Colitis | 55 Participants | 10 Participants | 23 Participants | 22 Participants |
| Disease Location GA28948 Population Left-Sided Colitis | 217 Participants | 44 Participants | 84 Participants | 89 Participants |
| Disease Location GA28948 Population Pancolitis | 86 Participants | 18 Participants | 35 Participants | 33 Participants |
| Ethnicity (NIH/OMB) GA28948 & GA28949 Pooled Population Hispanic or Latino | 66 Participants | 13 Participants | 27 Participants | 26 Participants |
| Ethnicity (NIH/OMB) GA28948 & GA28949 Pooled Population Not Hispanic or Latino | 639 Participants | 130 Participants | 253 Participants | 256 Participants |
| Ethnicity (NIH/OMB) GA28948 & GA28949 Pooled Population Unknown or Not Reported | 11 Participants | 1 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) GA28948 Population Hispanic or Latino | 38 Participants | 8 Participants | 16 Participants | 14 Participants |
| Ethnicity (NIH/OMB) GA28948 Population Not Hispanic or Latino | 314 Participants | 63 Participants | 123 Participants | 128 Participants |
| Ethnicity (NIH/OMB) GA28948 Population Unknown or Not Reported | 6 Participants | 1 Participants | 3 Participants | 2 Participants |
| Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline GA28948 & GA28949 Pooled Population MCS ≥10 | 235 Participants | 51 Participants | 93 Participants | 91 Participants |
| Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline GA28948 & GA28949 Pooled Population MCS ≤9 | 481 Participants | 93 Participants | 192 Participants | 196 Participants |
| Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline GA28948 Population MCS ≥10 | 115 Participants | 25 Participants | 46 Participants | 44 Participants |
| Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline GA28948 Population MCS ≤9 | 243 Participants | 47 Participants | 96 Participants | 100 Participants |
| Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline GA28948 & GA28949 Pooled Population Missing | 43 Participants | 3 Participants | 17 Participants | 23 Participants |
| Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline GA28948 & GA28949 Pooled Population NHI Score ≤1 | 91 Participants | 17 Participants | 38 Participants | 36 Participants |
| Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline GA28948 & GA28949 Pooled Population NHI Score >1 | 582 Participants | 124 Participants | 230 Participants | 228 Participants |
| Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline GA28948 Population Missing | 22 Participants | 2 Participants | 11 Participants | 9 Participants |
| Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline GA28948 Population NHI Score ≤1 | 38 Participants | 8 Participants | 15 Participants | 15 Participants |
| Nancy Histological Index (NHI) Score of ≤1 or >1, or Missing, at Baseline GA28948 Population NHI Score >1 | 298 Participants | 62 Participants | 116 Participants | 120 Participants |
| Race/Ethnicity, Customized GA28948 & GA28949 Pooled Population Asian | 14 Participants | 4 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized GA28948 & GA28949 Pooled Population Black or African American | 9 Participants | 3 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized GA28948 & GA28949 Pooled Population Other | 28 Participants | 4 Participants | 14 Participants | 10 Participants |
| Race/Ethnicity, Customized GA28948 & GA28949 Pooled Population White | 665 Participants | 133 Participants | 261 Participants | 271 Participants |
| Race/Ethnicity, Customized GA28948 Population Asian | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized GA28948 Population Black or African American | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized GA28948 Population Other | 17 Participants | 2 Participants | 10 Participants | 5 Participants |
| Race/Ethnicity, Customized GA28948 Population White | 336 Participants | 68 Participants | 130 Participants | 138 Participants |
| Sex: Female, Male GA28948 & GA28949 Pooled Population Female | 318 Participants | 67 Participants | 122 Participants | 129 Participants |
| Sex: Female, Male GA28948 & GA28949 Pooled Population Male | 398 Participants | 77 Participants | 163 Participants | 158 Participants |
| Sex: Female, Male GA28948 Population Female | 163 Participants | 33 Participants | 60 Participants | 70 Participants |
| Sex: Female, Male GA28948 Population Male | 195 Participants | 39 Participants | 82 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 142 | 1 / 144 |
| other Total, other adverse events | 7 / 72 | 17 / 142 | 6 / 144 |
| serious Total, serious adverse events | 2 / 72 | 3 / 142 | 8 / 144 |
Outcome results
Primary
Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28948 Population | 6.9 Percentage of participants |
| Etrolizumab | Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28948 Population | 19.4 Percentage of participants |
Comparison: 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.p-value: 0.017395% CI: [1.59, 20.6]Cochran-Mantel-Haenszel
Secondary
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
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.
Time frame: Baseline, Week 10
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | 38.4 Score on a scale | Standard Deviation 35.7 |
| Etrolizumab | 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 | 39.2 Score on a scale | Standard Deviation 32.8 |
| Etrolizumab | 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 | 39.8 Score on a scale | Standard Deviation 35.3 |
Comparison: 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.p-value: 0.791995% CI: [-8.3, 10.8]ANCOVA
Comparison: 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.p-value: 0.832795% CI: [-8.7, 7]ANCOVA
Secondary
Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28948 Population
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.
Time frame: Baseline, Week 6
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28948 Population | -1.0 Score on a scale |
| Etrolizumab | Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28948 Population | -1.0 Score on a scale |
| Etrolizumab | Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28948 Population | -1.0 Score on a scale |
Comparison: 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.p-value: 0.4434Rank ANCOVA
Comparison: 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.p-value: 0.3374Rank ANCOVA
Secondary
Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population | -1.0 Score on a scale |
| Etrolizumab | Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population | -1.0 Score on a scale |
Comparison: 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.p-value: 1Rank ANCOVA
Secondary
Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28948 Population
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.
Time frame: Baseline, Week 6
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28948 Population | 0.0 Score on a scale |
| Etrolizumab | Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28948 Population | -1.0 Score on a scale |
| Etrolizumab | Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28948 Population | -1.0 Score on a scale |
Comparison: 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.p-value: 0.4434Rank ANCOVA
Comparison: 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.p-value: 0.6367Rank ANCOVA
Secondary
Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population | -1.0 Score on a scale |
| Etrolizumab | Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population | -1.0 Score on a scale |
Comparison: 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.p-value: 1Rank ANCOVA
Secondary
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
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.
Time frame: Baseline, Week 10
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | -5.0 Score on a scale | Standard Error 0.5 |
| Etrolizumab | 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 | -5.8 Score on a scale | Standard Error 0.4 |
| Etrolizumab | 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 | -6.0 Score on a scale | Standard Error 0.3 |
Comparison: 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.p-value: 195% CI: [-2.1, 0.2]Mixed Model for Repeated Measures
Comparison: 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.p-value: 195% CI: [-1.2, 0.7]Mixed Model for Repeated Measures
Secondary
Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population
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.
Time frame: Baseline, Week 10
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population | -1.4 Score on a scale | Standard Error 0.2 |
| Etrolizumab | Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population | -1.6 Score on a scale | Standard Error 0.2 |
| Etrolizumab | Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population | -1.9 Score on a scale | Standard Error 0.2 |
Comparison: 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.p-value: 195% CI: [-1, 0]Mixed Model for Repeated Measures
Comparison: 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.p-value: 195% CI: [-0.7, 0.1]Mixed Model for Repeated Measures
Secondary
Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 Population
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.
Time frame: Baseline, Week 10
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 Population | -1.7 Score on a scale | Standard Error 0.3 |
| Etrolizumab | Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 Population | -1.5 Score on a scale | Standard Error 0.2 |
| Etrolizumab | Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 Population | -1.9 Score on a scale | Standard Error 0.2 |
Comparison: 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.p-value: 0.635695% CI: [-0.9, 0.5]Mixed Model for Repeated Measures
Comparison: 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.p-value: 0.125395% CI: [-1, 0.1]Mixed Model for Repeated Measures
Secondary
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
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.
Time frame: Baseline, Week 10
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | -5.5 Score on a scale | Standard Error 0.7 |
| Etrolizumab | 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 | -5.7 Score on a scale | Standard Error 0.5 |
| Etrolizumab | 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 | -6.2 Score on a scale | Standard Error 0.5 |
Comparison: 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.p-value: 0.370895% CI: [-2.4, 0.9]Mixed Model for Repeated Measures
Comparison: 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.p-value: 0.447795% CI: [-1.8, 0.8]Mixed Model for Repeated Measures
Secondary
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population
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.
Time frame: From Baseline up to Week 10
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - High to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - High to High | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Low to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Low to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Low to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Normal | 69 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Normal to Normal | 69 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to Normal | 67 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Normal | 55 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to High | 2 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - High to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to Normal | 68 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Low to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Missing | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - High to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Low to Missing | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to Normal | 67 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to High | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Low | 2 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to Missing | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Normal | 67 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Low to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Missing | 2 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Creatinine - Normal to Normal | 69 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Creatinine - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to Normal | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Direct Bilirubin - Normal to Normal | 68 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Direct Bilirubin - Normal to Missing | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Potassium - Normal to Normal | 69 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to High | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Potassium - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to Normal | 68 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Low to Normal | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to Missing | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to Missing | 2 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - High to Missing | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to Normal | 68 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - Normal to Normal | 69 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - High to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Low to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - Normal to Missing | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Normal | 67 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Low | 8 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to High | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to High | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - High to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - High to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Low | 9 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Low to Low | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - Normal to Normal | 138 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Missing | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Low to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Missing | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - High to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Normal | 132 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Creatinine - Normal to Normal | 139 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Low to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Missing | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Normal to Normal | 139 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to Normal | 139 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Creatinine - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to Missing | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to Missing | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Direct Bilirubin - Normal to Normal | 134 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to Normal | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - High to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Normal | 118 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - High to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Direct Bilirubin - Normal to Missing | 8 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Low to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Low to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Low to Normal | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to Missing | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Potassium - Normal to Normal | 139 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Normal | 132 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - High to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to Normal | 136 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Potassium - Normal to Missing | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to Normal | 139 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to Missing | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Low to Normal | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to Missing | 7 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - High to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Low to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Low | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Normal | 123 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to Normal | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Bicarbonate (CO2) - High to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - Normal to Normal | 138 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Blood Urea Nitrogen - High to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Calcium - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Low to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Low to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Chloride - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Creatinine - Normal to Normal | 138 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Creatinine - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Direct Bilirubin - Normal to Normal | 134 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Direct Bilirubin - Normal to Missing | 10 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Potassium - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Potassium - Normal to Missing | 7 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Sodium - High to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Total Bilirubin - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Normal | 136 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Protein, Total - High to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Low to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Albumin - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to Normal | 138 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alkaline Phosphatase - High to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to Normal | 138 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - Normal to Missing | 6 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Alanine Aminotransferase - High to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to Normal | 137 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Aspartate Aminotransferase - Normal to High | 0 Participants |
Secondary
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population
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
Time frame: From Baseline up to Week 10
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Normal | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - Normal to High | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Normal | 58 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Missing | 2 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Low to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Low | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Low | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - High to High | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Low to Normal | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Normal | 52 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Missing | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Ery. Mean Corpuscular Volume - Normal to Missing | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Missing | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - High to Normal | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Ery. Mean Corpuscular Volume - Normal to Normal | 66 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - Normal to Missing | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Missing | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Low to Normal | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to Missing | 8 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Low | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Low to Low | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Normal | 64 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Low | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to High | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Low to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Normal | 65 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to Normal | 60 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Low | 3 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to Missing | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Normal | 63 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Absolute Count (Abs) - Normal to Normal | 66 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to High | 1 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to High | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - High to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Missing | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - High to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to Normal | 2 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - High to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Missing | 6 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Low | 4 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Low to Normal | 0 Participants |
| Placebo | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Normal | 122 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - High to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Normal | 126 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Missing | 11 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Absolute Count (Abs) - Normal to Normal | 130 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - Normal to Missing | 11 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - High to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Low to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Low to Normal | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Missing | 13 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Low | 15 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Normal | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Low | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Normal | 109 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Missing | 11 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Low to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Low to Normal | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Low | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Missing | 11 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Ery. Mean Corpuscular Volume - Normal to Normal | 129 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Ery. Mean Corpuscular Volume - Normal to Missing | 13 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Low | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Normal | 115 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to High | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Missing | 11 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to Normal | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to High | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to Missing | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to Normal | 120 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to High | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to Missing | 13 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - High to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - High to High | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Low to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Low | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Normal | 127 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - High to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Low | 11 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - High to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to High | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - High to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Absolute Count (Abs) - Normal to Normal | 130 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Missing | 8 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Missing | 12 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Missing | 9 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to Normal | 9 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Normal | 124 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Low to Normal | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to Low | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - High to Missing | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Low to Normal | 3 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Normal to High | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to Normal | 122 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hematocrit - Low to Low | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Low | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to High | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - High to Normal | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - High to Normal | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Low | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Normal | 125 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Low to Low | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - Normal to Missing | 12 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Normal to Missing | 9 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Missing | 8 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - Normal to Missing | 9 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Ery. Mean Corpuscular Volume - Normal to Normal | 132 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Normal | 110 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | White Blood Cell Count - Normal to Normal | 132 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Ery. Mean Corpuscular Volume - Normal to Missing | 12 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Normal to Low | 5 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Platelets - High to Normal | 4 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Low to Normal | 2 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Missing | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Eosinophils Abs - Normal to High | 1 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Low | 0 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Hemoglobin - Low to Normal | 9 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Lymphocytes Abs - Low to Normal | 7 Participants |
| Etrolizumab | Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28948 Population | Neutrophils, Total, Abs - Normal to Normal | 118 Participants |
Secondary
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population
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).
Time frame: Pre-dose (0 hour) on Day 1 and Week 4, Week 10, Week 14, and early termination/end of safety follow-up (up to 26 weeks)
Population: 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. The analysis of ADAs at baseline and post-baseline only included participants who received treatment with etrolizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Positive for ADAs at Baseline (BL) | 6 Participants |
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Negative for ADAs at BL | 138 Participants |
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Post-BL: Positive for Treatment Emergent ADAs | 27 Participants |
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Post-BL ADA Positive: Treatment-Induced ADAs | 27 Participants |
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Post-BL ADA Positive: Treatment-Enhanced ADAs | 0 Participants |
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Post-BL: Negative for Treatment Emergent ADAs | 117 Participants |
| Placebo | Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28948 Population | Post-BL ADA Negative: Treatment Unaffected | 6 Participants |
Secondary
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
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).
Time frame: From Baseline until the end of study (up to 26 weeks)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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 | AE by Worst Severity, Grade 4 | 0 Participants |
| Placebo | 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 | Serious Infections | 2 Participants |
| Placebo | 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 | Injection Site Reactions | 0 Participants |
| Placebo | 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 | AE by Worst Severity, Grade 3 | 2 Participants |
| Placebo | 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 | AE by Worst Severity, Grade 2 | 13 Participants |
| Placebo | 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 | AE Leading to Study Treatment Discontinuation | 0 Participants |
| Placebo | 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 | Infections | 7 Participants |
| Placebo | 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 | AE by Worst Severity, Grade 1 | 11 Participants |
| Placebo | 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 | AE Leading to Dose Interruption | 0 Participants |
| Placebo | 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 | Any Adverse Event (AE) | 26 Participants |
| Placebo | 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 | Related AE | 4 Participants |
| Placebo | 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 | Gastrointestinal Infections | 1 Participants |
| Placebo | 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 | Confirmed PML | 0 Participants |
| Placebo | 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 | Any AEs of Special Interest | 0 Participants |
| Placebo | 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 | Opportunistic Infections | 0 Participants |
| Placebo | 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 | Serious AE | 2 Participants |
| Placebo | 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 | AE by Worst Severity, Grade 5 | 0 Participants |
| Placebo | 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 | Malignancies | 0 Participants |
| Placebo | 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 | AE with Fatal Outcome | 0 Participants |
| Etrolizumab | 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 | Any AEs of Special Interest | 0 Participants |
| Etrolizumab | 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 | Any Adverse Event (AE) | 61 Participants |
| Etrolizumab | 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 | AE with Fatal Outcome | 0 Participants |
| Etrolizumab | 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 | Serious AE | 3 Participants |
| Etrolizumab | 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 | Serious Infections | 0 Participants |
| Etrolizumab | 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 | Gastrointestinal Infections | 0 Participants |
| Etrolizumab | 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 | Opportunistic Infections | 0 Participants |
| Etrolizumab | 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 | Malignancies | 0 Participants |
| Etrolizumab | 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 | Injection Site Reactions | 4 Participants |
| Etrolizumab | 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 | AE Leading to Study Treatment Discontinuation | 2 Participants |
| Etrolizumab | 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 | AE Leading to Dose Interruption | 1 Participants |
| Etrolizumab | 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 | Related AE | 14 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 1 | 33 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 2 | 22 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 3 | 6 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 4 | 0 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 5 | 0 Participants |
| Etrolizumab | 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 | Confirmed PML | 0 Participants |
| Etrolizumab | 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 | Infections | 17 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 2 | 18 Participants |
| Etrolizumab | 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 | Injection Site Reactions | 1 Participants |
| Etrolizumab | 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 | Infections | 15 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 3 | 9 Participants |
| Etrolizumab | 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 | Malignancies | 0 Participants |
| Etrolizumab | 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 | Confirmed PML | 0 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 4 | 1 Participants |
| Etrolizumab | 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 | Opportunistic Infections | 0 Participants |
| Etrolizumab | 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 | Any Adverse Event (AE) | 50 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 5 | 1 Participants |
| Etrolizumab | 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 | Gastrointestinal Infections | 1 Participants |
| Etrolizumab | 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 | AE Leading to Dose Interruption | 3 Participants |
| Etrolizumab | 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 | Serious Infections | 2 Participants |
| Etrolizumab | 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 | Related AE | 10 Participants |
| Etrolizumab | 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 | AE Leading to Study Treatment Discontinuation | 2 Participants |
| Etrolizumab | 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 | Any AEs of Special Interest | 0 Participants |
| Etrolizumab | 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 | AE by Worst Severity, Grade 1 | 21 Participants |
| Etrolizumab | 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 | Serious AE | 8 Participants |
| Etrolizumab | 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 | AE with Fatal Outcome | 1 Participants |
Secondary
Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28948 Population | 8.3 Percentage of participants |
| Etrolizumab | Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28948 Population | 23.9 Percentage of participants |
| Etrolizumab | Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28948 Population | 19.4 Percentage of participants |
Comparison: 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.p-value: 0.036495% CI: [-0.08, 19.48]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.338395% CI: [-14.1, 5.07]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | 6.9 Percentage of participants |
| Etrolizumab | Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | 20.4 Percentage of participants |
| Etrolizumab | Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | 20.8 Percentage of participants |
Comparison: 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.p-value: 0.134795% CI: [2.97, 22.15]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.913895% CI: [-8.95, 9.92]Cochran-Mantel-Haenszel
Secondary
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
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.
Time frame: Week 10
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 23.5 Percentage of participants |
| Etrolizumab | 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 | 20.2 Percentage of participants |
Comparison: 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.p-value: 195% CI: [-10.27, 3.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28948 Population
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.
Time frame: Weeks 10 and 14
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28948 Population | 2.8 Percentage of participants |
| Etrolizumab | Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28948 Population | 12.7 Percentage of participants |
| Etrolizumab | Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28948 Population | 9.0 Percentage of participants |
Comparison: 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.p-value: 0.0995% CI: [-3.33, 12.3]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.321795% CI: [-11.07, 3.78]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population
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.
Time frame: Week 10
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population | 23.5 Percentage of participants |
| Etrolizumab | Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population | 18.8 Percentage of participants |
Comparison: 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.p-value: 195% CI: [-11.66, 1.75]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 Population | 22.5 Percentage of participants |
| Etrolizumab | Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 Population | 19.4 Percentage of participants |
Comparison: 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.p-value: 0.505595% CI: [-12.61, 6.37]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28948 Population | 50.0 Percentage of participants |
| Etrolizumab | Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28948 Population | 52.1 Percentage of participants |
| Etrolizumab | Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28948 Population | 56.9 Percentage of participants |
Comparison: 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.p-value: 0.443495% CI: [-7.03, 20.62]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.412295% CI: [-6.72, 16.07]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population
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.
Time frame: Week 10
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population | 53.3 Percentage of participants |
| Etrolizumab | Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population | 54.7 Percentage of participants |
Comparison: 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.p-value: 195% CI: [-6.98, 9.26]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28948 Population | 16.1 Percentage of participants |
| Etrolizumab | Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28948 Population | 29.3 Percentage of participants |
| Etrolizumab | Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28948 Population | 42.5 Percentage of participants |
Comparison: 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.p-value: 0.017395% CI: [12.1, 37.86]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.031395% CI: [0.93, 24.94]Cochran-Mantel-Haenszel
Secondary
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
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 36.5 Percentage of participants |
| Etrolizumab | 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 | 36.8 Percentage of participants |
Comparison: 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.p-value: 195% CI: [-9.13, 8.45]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population
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.
Time frame: Week 10
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | 22.2 Percentage of participants |
| Etrolizumab | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | 33.1 Percentage of participants |
| Etrolizumab | Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the MCS Endoscopy Subscore, GA28948 Population | 40.3 Percentage of participants |
Comparison: 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.p-value: 0.017395% CI: [4.49, 29.5]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.188695% CI: [-3.77, 18.32]Cochran-Mantel-Haenszel
Secondary
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
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.
Time frame: Week 10
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 37.9 Percentage of participants |
| Etrolizumab | 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 | 40.1 Percentage of participants |
Comparison: 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.p-value: 195% CI: [-6.04, 9.88]Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics of Etrolizumab: Serum Concentration, GA28948 Population
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.
Time frame: Weeks 10 and 14
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics of Etrolizumab: Serum Concentration, GA28948 Population | Week 10 | 13.0 micrograms per millilitre (μg/mL) | Standard Deviation 5.84 |
| Placebo | Pharmacokinetics of Etrolizumab: Serum Concentration, GA28948 Population | Week 14 | 17.1 micrograms per millilitre (μg/mL) | Standard Deviation 8.1 |