HICKORY: A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02100696
Collaborator
(none)
609
184
6
70.9
3.3
0
Study Details
Study Description
Brief Summary
This Phase III, double-blind, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab during induction and maintenance of remission compared with placebo in the treatment of participants with moderately to severely active ulcerative colitis (UC) who have been previously exposed to TNF inhibitors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
609 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Phase III, Double-Blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Etrolizumab During Induction and Maintenance in Patients With Moderate to Severe Active Ulcerative Colitis Who Have Been Previously Exposed to TNF Inhibitors
Actual Study Start Date
:
May 21, 2014
Actual Primary Completion Date
:
Apr 16, 2020
Actual Study Completion Date
:
Apr 16, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. |
Drug: Etrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
Other Names:
|
| Placebo Comparator: Cohort 2: Placebo (Double-Blind Induction Phase) Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. |
Drug: Placebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
|
| Experimental: Cohort 2: Etrolizumab (Double-Blind Induction Phase) Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
Drug: Etrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
Other Names:
|
| Placebo Comparator: Placebo Responders: Placebo (Maintenance Phase) Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. |
Drug: Placebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
|
| Placebo Comparator: Etrolizumab Responders: Placebo (Maintenance Phase) Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. |
Drug: Placebo
Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
|
| Experimental: Etrolizumab Responders: Etrolizumab (Maintenance Phase) Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
Drug: Etrozulimab
Participants will receive 105 mg etrolizumab administered by SC injection Q4W.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) [Week 14]
The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0.
- Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved a Clinical Response at Week 14, as Determined by the MCS [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Secondary Outcome Measures
- Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS [Week 14]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Clinical Remission is MCS ≤2 with individual subscores ≤1.
- Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS [Week 14]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
- Induction Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 14, as Determined by the MCS Endoscopic Subscore [Baseline and Week 14]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
- Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore [Week 14]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0.
- Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index [Week 14]
Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1.
- Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore [Baseline and 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.
- Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore [Baseline and 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.
- Induction Phase: Change From Baseline to Week 14 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire [Baseline and Week 14]
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.
- Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire [Baseline and Week 14]
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.
- Induction Phase: Change From Baseline to Week 14 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ) [Baseline and Week 14]
The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.
- Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 Among Participants Who Had Achieved Clinical Remission at Week 14, as Determined by the MCS [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1.
- Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1.
- Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0.
- Maintenance Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 66, as Determined by the MCS Endoscopic Subscore [Baseline and Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
- Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index [Week 66]
Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1.
- Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0.
- Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66.
- Maintenance Phase: Percentage of Participants With Corticosteroid-Free Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [Week 66]
The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66.
- Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire [Baseline and Week 66]
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.
- Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire [Baseline and Week 66]
The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.
- Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ [Baseline and Week 66]
The IBDQ is used to assess participant's health-related quality of life (QOL). The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.
- Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) [From Baseline up to Week 78]
All Adverse Events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
- Number of Participants With Adverse Events Leading to Study Drug Discontinuation [From Baseline up to Week 78]
- Number of Participants With Serious Infection-Related Adverse Events [From Baseline up to Week 78]
- Number of Participants With Infection-Related Adverse Events [From Baseline up to Week 78]
All Adverse Events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
- Number of Participants With Injection-Site Reaction-Related Adverse Events [From Baseline up to Week 78]
- Number of Participants With Hypersensitivity Reaction-Related Adverse Events [From Baseline up to Week 78]
- Number of Participants With Malignancies [From Baseline up to Week 78]
- Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study [Pre-dose at Baseline, Weeks 4, 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78)]
A tiered strategy was used to detect and characterize etrolizumab antibodies within this clinical study. When determining post baseline incidence, participants were considered to be ADA positive 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 unit 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).
- Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) [Pre-dose (0 hour) at Baseline and Weeks 14, 24, 44 and 66]
As per Protocol, the timepoints for each arm where more than a third of the samples were above the lower limit of quantification (LLOQ), full summary statistics (Mean and Standard Deviation) were reported. For timepoints below the LLOQ, only the Median and Max were reported as a separate outcome measure below.
- Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ) [Weeks 44 and 66]
As per Protocol, the timepoints for each arm where more than a third of the samples were below the LLOQ only the Median and Max were reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of UC established at least 3 months prior to Day 1
-
Moderately to severely active UC as determined by the Mayo Clinic Score (MCS) assessment
-
Treatment within 5 years prior to screening with one or two induction regimens that contain TNF inhibitors (including TNF inhibitor biosimilars)
-
Washout of anti-TNF therapy for at least 8 weeks preceding Day 1
-
Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
-
Use of highly effective contraception as defined by the protocol
-
Must have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening
Exclusion Criteria:
-
A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic colitis, radiation colitis, or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps
-
Prior or planned surgery for UC
-
Past or present ileostomy or colostomy
-
Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab)
-
Any prior treatment with anti-adhesion molecules (e.g. anti-MAdCAM-1)
-
Any prior treatment with rituximab
-
Any treatment with tofacitinib during screening
-
Congenital or acquired immune deficiency, chronic hepatitis B or C infection, human immunodeficiency virus (HIV) positive, or history of tuberculosis (active or latent)
-
Evidence of or treatment for Clostridium difficile or clinically significant cytomegalovirus (CMV) colitis within 60 days prior to Day 1
-
Evidence of or treatment for other intestinal pathogens within 30 days prior to Day 1
-
History of recurrent opportunistic infections and/or severe disseminated viral infections
-
History of organ transplant
-
Any major episode of infection requiring treatment with intravenous (IV) antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
-
Received a live attenuated vaccine within 4 weeks prior to Day 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294 |
| 2 | University of California San Diego Medical Center | La Jolla | California | United States | 92093-5354 |
| 3 | Clinical Applications Laboratories, Inc. | San Diego | California | United States | 92103 |
| 4 | Precision Research Institute, LLC | San Diego | California | United States | 92114 |
| 5 | University of California at San Francisco | San Francisco | California | United States | 94115 |
| 6 | Rocky Mountain Gastroenterology Associates | Denver | Colorado | United States | 80222 |
| 7 | Rocky Mountain Gastroenterology Associates, P.L.L.C.; Gastroenterology | Lakewood | Colorado | United States | 80215 |
| 8 | FQL Research, LLC | Miramar | Florida | United States | 33025 |
| 9 | Center For Digestive Health | Orlando | Florida | United States | 32803 |
| 10 | Internal Medicine Specialists | Orlando | Florida | United States | 32806 |
| 11 | Shafran Gastroenterology Center | Winter Park | Florida | United States | 32789 |
| 12 | Gastroenterology Associates of Central Georgia | Macon | Georgia | United States | 31201 |
| 13 | Gastrointestinal Specialists of Georgia, PC | Marietta | Georgia | United States | 30060 |
| 14 | Atlanta Gastroenterology Specialists, PC | Suwanee | Georgia | United States | 30024 |
| 15 | Northwestern University Feinberg School Of Medicine | Chicago | Illinois | United States | 60611 |
| 16 | Southwest Gastroenterology | Oak Lawn | Illinois | United States | 60453 |
| 17 | Cotton-O'Neil Clinical Research Center, Digestive Health | Topeka | Kansas | United States | 66606 |
| 18 | Gastroenterology Associates, LLC | Baton Rouge | Louisiana | United States | 70809 |
| 19 | Louisiana Research Center, LLC | Shreveport | Louisiana | United States | |
| 20 | Massachusetts General Hospital; Crohn's & Colitis Center | Boston | Massachusetts | United States | 02114 |
| 21 | University of Michigan; Michigan Institute for Clinical and Health Research (MICHR) | Ann Arbor | Michigan | United States | 48109 |
| 22 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
| 23 | Center for Digestive Health | Troy | Michigan | United States | 48098 |
| 24 | Kansas City Research Institute, LLC | Kansas City | Missouri | United States | 64131 |
| 25 | Clinica Peruano Americana S.A. | Great Neck | New York | United States | 11021 |
| 26 | Weill Cornell Medical College-New York Presbyterian Hospital | New York | New York | United States | 10021 |
| 27 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 28 | Consultants for Clinical Research Inc. | Cincinnati | Ohio | United States | 45219 |
| 29 | UC Health, LLC. | Cincinnati | Ohio | United States | 45219 |
| 30 | Great Lakes Gastroenterology Research, LLC | Mentor | Ohio | United States | 44060 |
| 31 | Gastroenterology Center of the Midsouth, P.C. | Memphis | Tennessee | United States | 38120 |
| 32 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 33 | Tyler Research Institute, LLC | Tyler | Texas | United States | 75701 |
| 34 | Ericksen Research and Development | Clinton | Utah | United States | 84015 |
| 35 | University of Utah School of Medicine | Salt Lake City | Utah | United States | 84132 |
| 36 | Digestive and Liver Disease Specialists, Ltd. | Norfolk | Virginia | United States | 23502 |
| 37 | McGuire Research Institute; Gastroenterology | Richmond | Virginia | United States | 23249 |
| 38 | Washington Gastroenterology | Bellevue | Washington | United States | 98004 |
| 39 | Hospital Provincial del Centenario | Rosario | Argentina | 2000 | |
| 40 | Royal Brisbane and Women's Hospital | Herston | Queensland | Australia | 4029 |
| 41 | Mater Adult Hospital | South Brisbane | Queensland | Australia | 4101 |
| 42 | Princess Alexandra Hospital | Woolloongabba | Queensland | Australia | 4102 |
| 43 | Launceston General Hospital; Gastroenterology Research | Launceston | Tasmania | Australia | 7250 |
| 44 | St Vincent's Hospital Melbourne | Fitzroy | Victoria | Australia | 3065 |
| 45 | Footscray Hospital; Gastroenterology | Footscray | Victoria | Australia | 3011 |
| 46 | St Frances Xavier Cabrini Hospital | Malvern | Victoria | Australia | 3144 |
| 47 | Fiona Stanley Hospital | Murdoch | Western Australia | Australia | 6150 |
| 48 | Klinikum Klagenfurt am Wörtersee; Acute geriatric care | Klagenfurt | Austria | 9020 | |
| 49 | LKH - Universitätsklinikum der PMU Salzburg | Salzburg | Austria | 5020 | |
| 50 | Medizinische Universität Wien | Wien | Austria | 1090 | |
| 51 | Imeldaziekenhuis | Bonheiden | Belgium | 2820 | |
| 52 | CHU St Pierre (St Pierre) | Brussels | Belgium | 1000 | |
| 53 | UZ Brussel | Brussel | Belgium | 1090 | |
| 54 | UZ Gent | Gent | Belgium | 9000 | |
| 55 | AZ Sint Elisabeth Herentals | Herentals | Belgium | 2200 | |
| 56 | UZ Leuven; Neurology | Leuven | Belgium | 3000 | |
| 57 | CHU de Liège; Tour de Pathologie | Liège | Belgium | 4000 | |
| 58 | AZ Delta (Stedelijk Ziekenhuis) | Roeselare | Belgium | 8800 | |
| 59 | Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda | Goiânia | GO | Brazil | 74535-170 |
| 60 | Hospital Felicio Rocho | Belo Horizonte | MG | Brazil | 30110-068 |
| 61 | Centro Digestivo de Curitiba | Curitiba | PR | Brazil | 80430-160 |
| 62 | Hospital Universitario Clementino Fraga Filho - UFRJ | Rio de Janeiro | RJ | Brazil | 21941-913 |
| 63 | Hospital Moinhos de Vento | Porto Alegre | RS | Brazil | 90035-001 |
| 64 | Hospital de Clínicas de Porto Alegre X | Porto Alegre | RS | Brazil | |
| 65 | UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu | Botucatu | SP | Brazil | 18618-970 |
| 66 | CAEP - Centro Avancado de Estudos e Pesquisas Ltda. | Campinas | SP | Brazil | 13087-567 |
| 67 | Hospital Estadual Mario Covas | Santo Andre | SP | Brazil | 09190-610 |
| 68 | University of Calgary; Heritage Medical Research Clinic | Calgary | Alberta | Canada | T2N 4Z6 |
| 69 | Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology | Edmonton | Alberta | Canada | T6G 2X8 |
| 70 | Pacific Gastroenterology Associates | Vancouver | British Columbia | Canada | V6Z 2K5 |
| 71 | Queen Elizabeth II Health Sciences Centre; Gastroenterology Research | Halifax | Nova Scotia | Canada | B3H 1V7 |
| 72 | Taunton Health Centre | Oshawa | Ontario | Canada | L1H 7K4 |
| 73 | Mount Sinai Hospital | Toronto | Ontario | Canada | M5G 1X5 |
| 74 | Toronto Liver Centre | Toronto | Ontario | Canada | M6H 3M1 |
| 75 | Toronto Digestive Disease Associates | Vaughan | Ontario | Canada | L4L 4Y7 |
| 76 | Hotel Dieu de Levis | Levis | Quebec | Canada | G6V 3Z1 |
| 77 | Hôpital Maisonneuve - Rosemont | Montreal | Quebec | Canada | H1T 2M4 |
| 78 | Fakultni nemocnice Brno; Interni kardiologicka klinika | Brno | Czechia | 625 00 | |
| 79 | Hepato-Gastroenterologie HK, s.r.o. | Hradec Kralove | Czechia | 500 12 | |
| 80 | Pardubicka krajska nemocnice, a.s. | Pardubice | Czechia | 532 03 | |
| 81 | Nemocnice Na Bulovce | Prague | Czechia | 180 01 | |
| 82 | ISCARE a.s. | Praha 7 | Czechia | 170 04 | |
| 83 | Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni | Usti Nad Labem | Czechia | 401 13 | |
| 84 | Rigshospitalet; Medicinsk gastroenterologisk klinik | København Ø | Denmark | 2100 | |
| 85 | Ålborg Universitets Hospital; Gastromedicinsk | Ålborg | Denmark | 9000 | |
| 86 | CHU Amiens - Hopital Sud; Pharmacie - Secteur des Essais cliniques | Amiens Cedex01 | France | 80054 | |
| 87 | Hôpital Beaujon | Clichy cedex | France | 92110 | |
| 88 | Hopital Claude Huriez - CHU Lille | Lille | France | 59037 | |
| 89 | Hôpital Nord - CHU Marseille; Gastroenterology and Hepatology | Marseille cedex 20 | France | 13915 | |
| 90 | CHU Nice - Hopital de l'Archet 2 | Nice | France | 06202 | |
| 91 | Hôpital Saint-Louis | Paris | France | 75475 | |
| 92 | Groupe Hospitalier Sud - Hôpital Haut-Lévêque - USN | Pessac | France | 33604 | |
| 93 | CHU Saint Etienne - Hôpital Nord | Saint Etienne | France | 42055 | |
| 94 | Höpital Hautepierre; Pediatrie1 | Strasbourg | France | 67098 | |
| 95 | CHU de Toulouse - Hôpital Rangueil | Toulouse Cedex 09 | France | 31059 | |
| 96 | Hôpital de Brabois Adultes | Vandoeuvre-les-nancy | France | 54511 | |
| 97 | Charite Universitaetsmedizin Berlin - Campus Charite Mitte | Berlin | Germany | 10117 | |
| 98 | DRK Kliniken Berlin Westend | Berlin | Germany | 14050 | |
| 99 | Universitaetsklinikum Erlangen | Erlangen | Germany | 91054 | |
| 100 | Klinikum der Johann Wolfgang Goethe-Universitaet | Frankfurt | Germany | 60590 | |
| 101 | Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation | Freiburg | Germany | 79106 | |
| 102 | Universitaetsklinikum Halle (Saale) | Halle | Germany | 06120 | |
| 103 | Hamburgisches Forschungsinstitut fuer CED | Hamburg | Germany | 20148 | |
| 104 | Universitätsklinikum Hamburg-Eppendorf | Hamburg | Germany | 20246 | |
| 105 | Gastroenterologie Eppendorfer Baum | Hamburg | Germany | 20249 | |
| 106 | Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie | Hannover | Germany | 30625 | |
| 107 | Universitaetsklinikum Schleswig-Holstein, Campus Kiel | Kiel | Germany | 24116 | |
| 108 | Klinikum Mannheim GmbH Universitätsklinikum | Mannheim | Germany | 68167 | |
| 109 | Universitaetsklinikum Muenster | Muenster | Germany | 48149 | |
| 110 | Universitaetsklinikum Ulm | Ulm | Germany | 89081 | |
| 111 | Anticancer Hospital of Thessaliniki " Theagenio" | Thessaloniki | Greece | 54007 | |
| 112 | Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza | Bekescsaba | Hungary | 5600 | |
| 113 | Obudai Egeszsegugyi Centrum Kft. | Budapest | Hungary | 1036 | |
| 114 | Semmelweis Egyetem | Budapest | Hungary | 1083 | |
| 115 | Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo | Budapest | Hungary | 1125 | |
| 116 | Pannonia Maganorvosi Centrum | Budapest | Hungary | 1135 | |
| 117 | Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely | Budapest | Hungary | H-1077 | |
| 118 | Debreceni Egyetem | Debrecen | Hungary | 4032 | |
| 119 | Markhot Ferenc Oktato Korhaz es Rendelointezet | Eger | Hungary | 3300 | |
| 120 | Petz Aladar Megyei Oktato Korhaz | Gyor | Hungary | 9024 | |
| 121 | Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat | Miskolc | Hungary | 3526 | |
| 122 | Pecsi Tudomanyegyetem | Pecs | Hungary | 7624 | |
| 123 | Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz | Székesfehérvár | Hungary | 8000 | |
| 124 | Shaare Zedek Medical Center | Jerusalem | Israel | 9103102 | |
| 125 | Hadassah University Hospital - Ein Kerem; Neurosurgery | Jerusalem | Israel | 9112001 | |
| 126 | Rabin Medical Center-Beilinson Campus; Gaucher Clinic, Genetics Institute | Petach Tiqwa | Israel | 49100 | |
| 127 | Kaplan Medical Center | Rehovot | Israel | 7610001 | |
| 128 | Assaf Harofeh | Rishon Lezion | Israel | 7505001 | |
| 129 | Azienda Ospedaliera S. Orsola-Malpighi | Bologna | Emilia-Romagna | Italy | 40138 |
| 130 | A.O.U. Policlinico di Modena | Modena | Emilia-Romagna | Italy | 40124 |
| 131 | Azienda Ospedaliera Universitaria Policlinico Tor Vergata | Roma | Lazio | Italy | 00133 |
| 132 | Azienda Ospedaliera San Camillo Forlanini | Roma | Lazio | Italy | 00152 |
| 133 | Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Roma | Lazio | Italy | 00168 |
| 134 | Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco) | Milano | Lombardia | Italy | |
| 135 | Ospedale di Circolo; Neuropsichiatria Infantile | Rho | Lombardia | Italy | 20017 |
| 136 | Istituto Clinico Humanitas | Rozzano (MI) | Lombardia | Italy | 20089 |
| 137 | I.R.C.C.S Policlinico San Donato | San Donato Milanese (MI) | Lombardia | Italy | 20097 |
| 138 | Azienda Ospedaliera Universitaria Careggi | Firenze | Toscana | Italy | 50141 |
| 139 | Azienda Ospedaliera Di Padova | Padova | Veneto | Italy | 35128 |
| 140 | Kyungpook National University Hospital; Opthalmology | Daegu | Korea, Republic of | 700-721 | |
| 141 | Korea University Ansan Hospital | Gyeonggi-do | Korea, Republic of | 15355 | |
| 142 | Seoul National University Bundang Hospital | Seongnam-si | Korea, Republic of | 13605 | |
| 143 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 144 | Severance Hospital, Yonsei University | Seoul | Korea, Republic of | 03722 | |
| 145 | Samsung Medical Center | Seoul | Korea, Republic of | 06531 | |
| 146 | Asan Medical Center. | Seoul | Korea, Republic of | 138-736 | |
| 147 | The Catholic University of Korea St. Vincent's Hospital | Suwon-si, | Korea, Republic of | 442-723 | |
| 148 | Hospital of Lithuanian University of Health. Sciences Kaunas Clinics | Kaunas | Lithuania | 50009 | |
| 149 | Vilnius University Hospital Santariskiu Clinic Public Insti | Vilnius | Lithuania | 08661 | |
| 150 | Centro Regiomontano de Estudios Clínicos Roma S.C. | Monterrey | Nuevo LEON | Mexico | 64610 |
| 151 | Amsterdam UMC, Locatie VUMC; Neurology | Amsterdam | Netherlands | 1081 HV | |
| 152 | Amsterdam UMC Location AMC | Amsterdam | Netherlands | 1105 AZ | |
| 153 | Rijnstate; Internal Medicine Department | Arnhem | Netherlands | 6815 AD | |
| 154 | Radboudumc | NL -nijmegen | Netherlands | 6525 GA | |
| 155 | Nasz Lekarz Osrodek Badan Klinicznych | Bydgoszcz | Poland | 85-312 | |
| 156 | Nzoz All-Medicus | Katowice | Poland | 40-660 | |
| 157 | Gabinet Lekarski, Bartosz Korczowski | Rzeszów | Poland | 35-302 | |
| 158 | Niepubliczny Zaklad Opieki Zdrowotnej SONOMED | Szczecin | Poland | 70-351 | |
| 159 | Centrum Zdrowia MDM | Warszawa | Poland | 00-631 | |
| 160 | Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy | Warszawa | Poland | 02-781 | |
| 161 | Nzoz Vivamed | Warszawa | Poland | 03-580 | |
| 162 | LexMedica Osrodek Badan Klinicznych | Wroclaw | Poland | 53-114 | |
| 163 | EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu | Wroclaw | Poland | 54-144 | |
| 164 | PlanetMed | Wrocław | Poland | 52-210 | |
| 165 | SC Euroclinic Hospital SA | Bucuresti | Romania | 014461 | |
| 166 | Fundacion Hospital de Alcorcon; Servicio de Digestivo | Alcorcon | Madrid | Spain | 28922 |
| 167 | Hospital Universitari de Girona Dr Josep Trueta | Girona | Spain | 17007 | |
| 168 | Hospital Universitario de la Princesa | Madrid | Spain | 28006 | |
| 169 | Hospital Universitario de Fuenlabrada | Madrid | Spain | 28942 | |
| 170 | Hospital Universitari i Politecnic La Fe | Valencia | Spain | 46026 | |
| 171 | Hospital Universitario Miguel Servet | Zaragoza | Spain | 50009 | |
| 172 | Inselspital-Universitaetsspital Bern; Institut fuer Spitalpharmazie | Bern | Switzerland | 3010 | |
| 173 | Cliniques Universitaires Saint-Luc; Nephrology | Bern | Switzerland | 3012 | |
| 174 | Crohn-Colitis Zentrum Bern - Gemeinschaftspraxis Balsiger, Seibold und Partner | Bern | Switzerland | 3012 | |
| 175 | Addenbrooke's Hospital | Cambridge | United Kingdom | CB2 0QQ | |
| 176 | Royal Devon and Exeter Hospital (Wonford) | Exeter | United Kingdom | EX2 5DW | |
| 177 | The Royal London Hospital | London | United Kingdom | E1 2ES | |
| 178 | University College London Hospital | London | United Kingdom | NW1 - 2PG | |
| 179 | St Thomas Hospital | London | United Kingdom | SE1 7EH | |
| 180 | King's College London | London | United Kingdom | SE5 9NU | |
| 181 | Fairfield General Hospital | Manchester | United Kingdom | M8 5RB | |
| 182 | Royal Victoria Infirmary | Newcastle upon Tyne | United Kingdom | NE1 4LP | |
| 183 | Nottingham University Hospitals; QMC Campus | Nottingham | United Kingdom | NG7 2UH | |
| 184 | Southampton General Hospital | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02100696
Other Study ID Numbers:
- GA28950
- 2013-004278-88
First Posted:
Apr 1, 2014
Last Update Posted:
Aug 13, 2021
Last Verified:
Jul 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 184 centers in 24 countries. |
|---|---|
| Pre-assignment Detail | A total of 609 participants were enrolled into the Induction phase of this study and the entire study. A subset (259) of these participants moved into the Maintenance phase of this study. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Period Title: Induction Phase | ||||||
| STARTED | 130 | 95 | 384 | 0 | 0 | 0 |
| COMPLETED | 115 | 90 | 358 | 0 | 0 | 0 |
| NOT COMPLETED | 15 | 5 | 26 | 0 | 0 | 0 |
| Period Title: Induction Phase | ||||||
| STARTED | 0 | 0 | 0 | 27 | 115 | 117 |
| COMPLETED | 0 | 0 | 0 | 26 | 106 | 112 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 9 | 5 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. | Total of all reporting groups |
| Overall Participants | 130 | 95 | 384 | 27 | 115 | 117 | 868 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
39.5
(13.5)
|
38.8
(13.9)
|
40.7
(13.3)
|
40.1
(13.4)
|
|||
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
43.1
(13.8)
|
42.0
(13.5)
|
40.0
(12.9)
|
41.2
(13.2)
|
|||
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
52
40%
|
41
43.2%
|
160
41.7%
|
253
937%
|
|||
| Male |
78
60%
|
54
56.8%
|
224
58.3%
|
356
1318.5%
|
|||
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
9
6.9%
|
43
45.3%
|
57
14.8%
|
109
403.7%
|
|||
| Male |
18
13.8%
|
72
75.8%
|
60
15.6%
|
150
555.6%
|
|||
| Race/Ethnicity, Customized (Number) [Number] | |||||||
| Hispanic or Latino |
4
3.1%
|
5
5.3%
|
30
7.8%
|
39
144.4%
|
|||
| Not Hispanic or Latino |
118
90.8%
|
76
80%
|
321
83.6%
|
515
1907.4%
|
|||
| Not Reported or Unknown |
8
6.2%
|
14
14.7%
|
33
8.6%
|
55
203.7%
|
|||
| American Indian or Alaska Native |
0
0%
|
1
1.1%
|
0
0%
|
1
3.7%
|
|||
| Asian |
6
4.6%
|
5
5.3%
|
26
6.8%
|
37
137%
|
|||
| Black or African American |
3
2.3%
|
1
1.1%
|
6
1.6%
|
10
37%
|
|||
| White |
109
83.8%
|
73
76.8%
|
304
79.2%
|
486
1800%
|
|||
| Other |
12
9.2%
|
15
15.8%
|
48
12.5%
|
75
277.8%
|
|||
| Race/Ethnicity, Customized (Number) [Number] | |||||||
| Hispanic or Latino |
1
0.8%
|
8
8.4%
|
9
2.3%
|
18
66.7%
|
|||
| Not Hispanic or Latino |
21
16.2%
|
95
100%
|
94
24.5%
|
210
777.8%
|
|||
| Not Reported or Unknown |
5
3.8%
|
12
12.6%
|
14
3.6%
|
31
114.8%
|
|||
| Asian |
2
1.5%
|
5
5.3%
|
5
1.3%
|
12
44.4%
|
|||
| Black or African American |
0
0%
|
1
1.1%
|
3
0.8%
|
4
14.8%
|
|||
| White |
20
15.4%
|
96
101.1%
|
92
24%
|
208
770.4%
|
|||
| Other |
5
3.8%
|
13
13.7%
|
17
4.4%
|
35
129.6%
|
|||
Outcome Measures
| Title | Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS) |
|---|---|
| Description | The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. |
| Time Frame | Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 95 | 384 |
| Number [Percentage of Participants] |
6.3
4.8%
|
18.5
19.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0033 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in response rates |
| Estimated Value | 12.2 | |
| Confidence Interval |
(2-Sided) 95% 3.95 to 17.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved a Clinical Response at Week 14, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 114 | 112 |
| Number [Percentage of Participants] |
20.2
15.5%
|
24.1
25.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4956 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 3.8 | |
| Confidence Interval |
(2-Sided) 95% -7.13 to 14.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Clinical Remission is MCS ≤2 with individual subscores ≤1. |
| Time Frame | Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 95 | 384 |
| Number [Percentage of Participants] |
6.3
4.8%
|
18.8
19.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0028 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 12.5 | |
| Confidence Interval |
(2-Sided) 95% 4.19 to 17.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. |
| Time Frame | Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 95 | 384 |
| Number [Percentage of Participants] |
31.6
24.3%
|
45.8
48.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0241 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Response Rates |
| Estimated Value | 14.3 | |
| Confidence Interval |
(2-Sided) 95% 3.21 to 24.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 14, as Determined by the MCS Endoscopic Subscore |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1. |
| Time Frame | Baseline and Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 95 | 384 |
| Number [Percentage of Participants] |
25.3
19.5%
|
33.3
35.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1605 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Response Rates |
| Estimated Value | 8.1 | |
| Confidence Interval |
(2-Sided) 95% -2.54 to 17.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0. |
| Time Frame | Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 95 | 384 |
| Number [Percentage of Participants] |
9.5
7.3%
|
17.2
18.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3881 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 7.6 | |
| Confidence Interval |
(2-Sided) 95% -1.22 to 13.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index |
|---|---|
| Description | Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1. |
| Time Frame | Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 80 | 310 |
| Number [Percentage of Participants] |
25.0
19.2%
|
29.7
31.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5879 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 4.9 | |
| Confidence Interval |
(2-Sided) 95% -6.78 to 14.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore |
|---|---|
| Description | 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 and Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 94 | 383 |
| Mean (Standard Deviation) [Score on a Scale] |
-0.4
(0.8)
|
-0.7
(0.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0351 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Unadjusted Means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to -0.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore |
|---|---|
| Description | 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 and Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 94 | 383 |
| Mean (Standard Deviation) [Score on a Scale] |
-0.5
(0.9)
|
-0.6
(1.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2698 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Unadjusted Means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Change From Baseline to Week 14 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire |
|---|---|
| Description | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. |
| Time Frame | Baseline and Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 80 | 272 |
| Least Squares Mean (Standard Error) [Score on a Scale] |
-3.6
(0.6)
|
-5.2
(0.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2698 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Least Square Means |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to -0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire |
|---|---|
| Description | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. |
| Time Frame | Baseline and Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 80 | 272 |
| Least Squares Mean (Standard Error) [Score on a Scale] |
-1.1
(0.2)
|
-1.5
(0.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3881 |
| Comments | Multiplicity P-value reported (adjusted for multiplicity) | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Least Square Means |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Induction Phase: Change From Baseline to Week 14 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ) |
|---|---|
| Description | The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. |
| Time Frame | Baseline and Week 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in Cohort 2 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Arm/Group Description | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. |
| Measure Participants | 74 | 293 |
| Least Squares Mean (Standard Error) [Scores on a Scale] |
28.4
(4.12)
|
37.4
(2.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0445 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Adjusted Means |
| Estimated Value | 9.1 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 17.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 Among Participants Who Had Achieved Clinical Remission at Week 14, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 44 | 42 |
| Number [Percentage of Participants] |
36.4
28%
|
38.1
40.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9959 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -19.67 to 19.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 114 | 112 |
| Number [Percentage of Participants] |
21.1
16.2%
|
25.0
26.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5014 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 3.8 | |
| Confidence Interval |
(2-Sided) 95% -7.26 to 14.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 44 | 41 |
| Number [Percentage of Participants] |
34.1
26.2%
|
36.6
38.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9538 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -19.08 to 20.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 66, as Determined by the MCS Endoscopic Subscore |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1. |
| Time Frame | Baseline and Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 114 | 112 |
| Number [Percentage of Participants] |
21.1
16.2%
|
35.7
37.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0153 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Response Rates |
| Estimated Value | 14.5 | |
| Confidence Interval |
(2-Sided) 95% 2.66 to 25.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index |
|---|---|
| Description | Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 92 | 91 |
| Number [Percentage of Participants] |
14.1
10.8%
|
30.8
32.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0073 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 16.8 | |
| Confidence Interval |
(2-Sided) 95% 4.44 to 28.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 114 | 112 |
| Number [Percentage of Participants] |
11.4
8.8%
|
23.2
24.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0174 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 11.9 | |
| Confidence Interval |
(2-Sided) 95% 1.87 to 21.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 55 | 54 |
| Number [Percentage of Participants] |
12.7
9.8%
|
20.4
21.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3015 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 7.3 | |
| Confidence Interval |
(2-Sided) 95% -6.83 to 21.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Percentage of Participants With Corticosteroid-Free Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS |
|---|---|
| Description | The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66. |
| Time Frame | Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 55 | 54 |
| Number [Percentage of Participants] |
10.9
8.4%
|
18.5
19.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2787 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference in Remission Rates |
| Estimated Value | 7.4 | |
| Confidence Interval |
(2-Sided) 95% -6.23 to 21.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire |
|---|---|
| Description | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. |
| Time Frame | Baseline and Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 83 | 83 |
| Least Squares Mean (Standard Error) [Score on a Scale] |
-6.3
(0.6)
|
-7.8
(0.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0763 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Least Square Means |
| Estimated Value | -1.5 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 0.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire |
|---|---|
| Description | The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. |
| Time Frame | Baseline and Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 83 | 83 |
| Least Squares Mean (Standard Error) [Score on a Scale] |
-1.8
(0.3)
|
-2.0
(0.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5329 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Least Square Means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ |
|---|---|
| Description | The IBDQ is used to assess participant's health-related quality of life (QOL). The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. |
| Time Frame | Baseline and Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-to-Treat (mITT) population was defined as all participants randomised in the maintenance phase who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomisation. Data presented below is only for participants included in the actual analysis. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 99 | 99 |
| Least Squares Mean (Standard Error) [Scores on a Scale] |
57.2
(3.1)
|
52.3
(3.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Placebo (Double-Blind Induction Phase), Cohort 2: Etrolizumab (Double-Blind Induction Phase) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2228 |
| Comments | Nominal P-value reported (not adjusted for multiplicity) | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Adjusted Means |
| Estimated Value | -4.9 | |
| Confidence Interval |
(2-Sided) 95% -12.7 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) |
|---|---|
| Description | All Adverse Events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Grade 1 |
39
30%
|
31
32.6%
|
117
30.5%
|
8
29.6%
|
19
16.5%
|
33
28.2%
|
| Grade 2 |
38
29.2%
|
26
27.4%
|
97
25.3%
|
14
51.9%
|
64
55.7%
|
45
38.5%
|
| Grade 3 |
15
11.5%
|
5
5.3%
|
37
9.6%
|
1
3.7%
|
14
12.2%
|
19
16.2%
|
| Grade 4 |
0
0%
|
1
1.1%
|
2
0.5%
|
0
0%
|
0
0%
|
1
0.9%
|
| Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Adverse Events Leading to Study Drug Discontinuation |
|---|---|
| Description | |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Number [Participants] |
2
1.5%
|
1
1.1%
|
12
3.1%
|
4
14.8%
|
9
7.8%
|
10
8.5%
|
| Title | Number of Participants With Serious Infection-Related Adverse Events |
|---|---|
| Description | |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Number [Participants] |
2
1.5%
|
1
1.1%
|
5
1.3%
|
0
0%
|
3
2.6%
|
3
2.6%
|
| Title | Number of Participants With Infection-Related Adverse Events |
|---|---|
| Description | All Adverse Events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Number [Participants] |
38
29.2%
|
29
30.5%
|
100
26%
|
13
48.1%
|
44
38.3%
|
58
49.6%
|
| Title | Number of Participants With Injection-Site Reaction-Related Adverse Events |
|---|---|
| Description | |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Number [Participants] |
7
5.4%
|
5
5.3%
|
4
1%
|
2
7.4%
|
2
1.7%
|
8
6.8%
|
| Title | Number of Participants With Hypersensitivity Reaction-Related Adverse Events |
|---|---|
| Description | |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Malignancies |
|---|---|
| Description | |
| Time Frame | From Baseline up to Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population was defined as all participants who received at least one dose of study drug during the induction and maintenance phases. Participants were grouped by cohort and included in the treatment arm for the treatment most frequently received during the induction and maintenance phases. |
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 130 | 95 | 384 | 27 | 114 | 112 |
| Number [Participants] |
0
0%
|
0
0%
|
2
0.5%
|
0
0%
|
0
0%
|
2
1.7%
|
| Title | Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study |
|---|---|
| Description | A tiered strategy was used to detect and characterize etrolizumab antibodies within this clinical study. When determining post baseline incidence, participants were considered to be ADA positive 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 unit 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 at Baseline, Weeks 4, 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result from at least one sample. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase. |
| Arm/Group Title | Cohort 1: Etrolizumab (OLI Phase) + Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|
| Arm/Group Description | Cohort 1: Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. Cohort 2: Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. Participants in this arm did not enter into the Maintenance phase of the study. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 286 | 114 | 112 |
| Baseline |
9
6.9%
|
2
2.1%
|
6
1.6%
|
| Post-Baseline |
68
52.3%
|
35
36.8%
|
28
7.3%
|
| Title | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ) |
|---|---|
| Description | As per Protocol, the timepoints for each arm where more than a third of the samples were above the lower limit of quantification (LLOQ), full summary statistics (Mean and Standard Deviation) were reported. For timepoints below the LLOQ, only the Median and Max were reported as a separate outcome measure below. |
| Time Frame | Pre-dose (0 hour) at Baseline and Weeks 14, 24, 44 and 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable PK data. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase. |
| Arm/Group Title | Cohort 1: Etrolizumab (OLI Phase) + Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) |
|---|---|---|---|
| Arm/Group Description | Cohort 1: Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. Cohort 2: Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. Participants in this arm did not enter into the Maintenance phase of the study. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 251 | 113 | 110 |
| Week 14 |
11.0
(4.66)
|
12.7
(5.50)
|
14.0
(6.12)
|
| Week 24 |
0.474
(0.742)
|
9.55
(5.24)
|
|
| Week 44 |
10.7
(5.72)
|
||
| Week 66 |
16.2
(7.75)
|
| Title | Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ) |
|---|---|
| Description | As per Protocol, the timepoints for each arm where more than a third of the samples were below the LLOQ only the Median and Max were reported. |
| Time Frame | Weeks 44 and 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable PK data and were part of the timepoints that had more than a third of samples below LLOQ. For the Induction Phase, data for Cohorts 1 and 2 are combined to present the Etrolizumab Induction data for participants not randomised into the Maintenance phase. |
| Arm/Group Title | Etrolizumab Responders: Placebo (Maintenance Phase) |
|---|---|
| Arm/Group Description | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. |
| Measure Participants | 113 |
| Week 44 |
0.0400
|
| Week 66 |
0.0400
|
Adverse Events
| Time Frame | Baseline up until a maximum of 78 weeks. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) | ||||||
| Arm/Group Description | Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase. | Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase. | Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66. | Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66. | ||||||
All Cause Mortality |
||||||||||||
| Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/130 (0%) | 0/95 (0%) | 0/384 (0%) | 0/27 (0%) | 0/114 (0%) | 0/112 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/130 (8.5%) | 5/95 (5.3%) | 20/384 (5.2%) | 2/27 (7.4%) | 7/114 (6.1%) | 11/112 (9.8%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 0/130 (0%) | 0 | 2/95 (2.1%) | 3 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 2/114 (1.8%) | 2 | 0/112 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Cheilitis | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Colitis ulcerative | 6/130 (4.6%) | 6 | 2/95 (2.1%) | 3 | 10/384 (2.6%) | 10 | 0/27 (0%) | 0 | 2/114 (1.8%) | 2 | 1/112 (0.9%) | 1 |
| Diarrhoea | 0/130 (0%) | 0 | 1/95 (1.1%) | 1 | 1/384 (0.3%) | 1 | 1/27 (3.7%) | 1 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Gastrointestinal necrosis | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Intestinal haemorrhage | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Pouchitis | 0/130 (0%) | 0 | 1/95 (1.1%) | 1 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| General disorders | ||||||||||||
| Oedema peripheral | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 1/114 (0.9%) | 1 | 0/112 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Abdominal abscess | 0/130 (0%) | 0 | 1/95 (1.1%) | 1 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Abscess | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Appendicitis | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 2/112 (1.8%) | 2 |
| Atypical pneumonia | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 1/114 (0.9%) | 1 | 0/112 (0%) | 0 |
| Clostridium difficile infection | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 1/114 (0.9%) | 1 | 0/112 (0%) | 0 |
| Cytomegalovirus infection | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 1/114 (0.9%) | 1 | 0/112 (0%) | 0 |
| Erysipelas | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Herpes zoster | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Influenza | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Osteomyelitis | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Pneumonia bacterial | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 1/114 (0.9%) | 1 | 0/112 (0%) | 0 |
| Tonsillitis | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Upper respiratory tract infection | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Viral infection | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Hypokalaemia | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Back pain | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Myalgia | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Basal cell carcinoma | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Pleomorphic adenoma | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Uteric cancer | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Hypoaesthesia | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Lethargy | 1/130 (0.8%) | 1 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Myoclonus | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| Affect liability | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Renal and urinary disorders | ||||||||||||
| Renal colic | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 1/27 (3.7%) | 1 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Asthma | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Eosinophilic pneumonia | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
| Vascular disorders | ||||||||||||
| Hypertension | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 1/384 (0.3%) | 1 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 1/112 (0.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase) | Cohort 2: Placebo (Double-Blind Induction Phase) | Cohort 2: Etrolizumab (Double-Blind Induction Phase) | Placebo Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Placebo (Maintenance Phase) | Etrolizumab Responders: Etrolizumab (Maintenance Phase) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/130 (29.2%) | 31/95 (32.6%) | 115/384 (29.9%) | 20/27 (74.1%) | 78/114 (68.4%) | 78/112 (69.6%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 1/27 (3.7%) | 1 | 7/114 (6.1%) | 7 | 10/112 (8.9%) | 11 |
| Colitis ulcerative | 9/130 (6.9%) | 9 | 10/95 (10.5%) | 10 | 36/384 (9.4%) | 37 | 11/27 (40.7%) | 11 | 46/114 (40.4%) | 52 | 31/112 (27.7%) | 32 |
| Diarrhoea | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 1/27 (3.7%) | 1 | 5/114 (4.4%) | 5 | 6/112 (5.4%) | 6 |
| Nausea | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 2/27 (7.4%) | 2 | 4/114 (3.5%) | 7 | 7/112 (6.3%) | 7 |
| General disorders | ||||||||||||
| Asthenia | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 2/27 (7.4%) | 3 | 3/114 (2.6%) | 3 | 5/112 (4.5%) | 6 |
| Fatigue | 8/130 (6.2%) | 11 | 1/95 (1.1%) | 1 | 10/384 (2.6%) | 13 | 1/27 (3.7%) | 1 | 4/114 (3.5%) | 4 | 12/112 (10.7%) | 13 |
| Injection site erythema | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 2/27 (7.4%) | 2 | 2/114 (1.8%) | 3 | 5/112 (4.5%) | 9 |
| Pyrexia | 5/130 (3.8%) | 7 | 6/95 (6.3%) | 8 | 3/384 (0.8%) | 3 | 0/27 (0%) | 0 | 0/114 (0%) | 0 | 0/112 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Gastroenteritis viral | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 1/114 (0.9%) | 1 | 6/112 (5.4%) | 6 |
| Influenza | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 1/27 (3.7%) | 1 | 9/114 (7.9%) | 9 | 5/112 (4.5%) | 5 |
| Nasopharyngitis | 12/130 (9.2%) | 12 | 7/95 (7.4%) | 8 | 33/384 (8.6%) | 35 | 4/27 (14.8%) | 5 | 17/114 (14.9%) | 22 | 23/112 (20.5%) | 33 |
| Oral herpes | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 2/27 (7.4%) | 2 | 1/114 (0.9%) | 1 | 5/112 (4.5%) | 6 |
| Upper respiratory tract infection | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 4/27 (14.8%) | 5 | 5/114 (4.4%) | 8 | 5/112 (4.5%) | 7 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 5/130 (3.8%) | 6 | 7/95 (7.4%) | 7 | 33/384 (8.6%) | 38 | 4/27 (14.8%) | 6 | 8/114 (7%) | 11 | 19/112 (17%) | 26 |
| Nervous system disorders | ||||||||||||
| Dizziness | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 2/27 (7.4%) | 2 | 1/114 (0.9%) | 1 | 2/112 (1.8%) | 2 |
| Headache | 10/130 (7.7%) | 11 | 6/95 (6.3%) | 8 | 22/384 (5.7%) | 26 | 3/27 (11.1%) | 3 | 10/114 (8.8%) | 12 | 10/112 (8.9%) | 10 |
| Psychiatric disorders | ||||||||||||
| Insomnia | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 2/114 (1.8%) | 2 | 6/112 (5.4%) | 8 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Pruritus | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 0/27 (0%) | 0 | 6/114 (5.3%) | 7 | 4/112 (3.6%) | 4 |
| Rash | 0/130 (0%) | 0 | 0/95 (0%) | 0 | 0/384 (0%) | 0 | 1/27 (3.7%) | 1 | 2/114 (1.8%) | 2 | 8/112 (7.1%) | 12 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800 821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02100696
Other Study ID Numbers:
- GA28950
- 2013-004278-88
First Posted:
Apr 1, 2014
Last Update Posted:
Aug 13, 2021
Last Verified:
Jul 1, 2021