Crohn's Disease
Conditions
Brief summary
This study in patients with moderately to severely active Crohn's disease is designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and remission.
Detailed description
After completing the study, patients were eligible to enroll in a long term safety study with continued access to vedolizumab (study C13008; NCT00790933) if study drug was well tolerated, and no major surgical intervention for Crohn's disease occurred or was required. Participants who did not enroll in Study C13008 were to complete the Final Safety visit (16 weeks after the last dose of study drug) for a maximum time on study of 22 weeks.
Interventions
DRUGvedolizumab
Vedolizumab for intravenous infusion
OTHERPlacebo
Placebo intravenous infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 * Diagnosis of moderately to severely active Crohn's disease * Crohn's Disease involvement of the ileum and/or colon * Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least one conventional therapy as defined by the protocol * May be receiving a therapeutic dose of conventional therapies for inflammatory bowel disease (IBD) as defined by the protocol
Exclusion criteria
* Evidence of abdominal abscess at the initial screening visit * Extensive colonic resection, subtotal or total colectomy * History of \>3 small bowel resections or diagnosis of short bowel syndrome * Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine * Have received non permitted therapies within either 30 or 60 days, depending on the medication, as stated in the protocol * Chronic hepatitis B or C infection; human immunodeficiency virus (HIV) infection * Active or latent tuberculosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation | Week 6 | Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation | Week 10 | Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission. |
| Percentage of Participants in Clinical Remission at Week 10 in the Overall Population | Week 10 | Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission. |
| Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population | Week 6 and Week 10 | Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission. |
| Percentage of Participants in Clinical Remission at Week 6 in the Overall Population | Week 6 | Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission. |
| Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation | Baseline and Week 6 | Enhanced clinical response is defined as a ≥ 100-point decrease in CDAI score from Baseline. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percent deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response. |
| Number of Participants With Adverse Events (AEs) | From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments. | An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was any AE, occurring at any dose and regardless of causality that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event based upon appropriate medical judgment that may have jeopardized the patient and may have required medical or surgical intervention to prevent 1 of the outcomes listed above, or any diagnosis of progressive multifocal leukoencephalopathy (PML). Relationship to study drug administration was determined by the investigator responding yes or no to the question: Is there a reasonable possibility that the AE is associated with the study drug? |
| Percentage of Participants With Sustained Clinical Remission in the Overall Population | Week 6 and Week 10 | Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants with moderately to severely active Crohn's Disease took part in the study at 107 sites worldwide from 24 November 2010 to 12 April 2012. Approximately 75% of participants were to have previously failed tumor necrosis factor alpha (TNFα) antagonist therapy and approximately 25% were to have been naïve to TNFα antagonist therapy.
Pre-assignment details
Participants were randomized 1:1 to receive either 300 mg vedolizumab or placebo. Randomization to treatment assignment was stratified by the presence or absence of previous failure of TNFα antagonist therapy or naïve to TNFα antagonist therapy, concomitant use of oral corticosteroids and concomitant use of immunomodulators.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo intravenous infusion at Weeks 0, 2 and 6. | 207 |
| Vedolizumab Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6. | 209 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Lack of Efficacy | 5 | 1 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal of Consent | 2 | 4 |
Baseline characteristics
| Characteristic | Total | Placebo | Vedolizumab |
|---|---|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 12.66 | 37.1 years STANDARD_DEVIATION 13.15 | 38.6 years STANDARD_DEVIATION 12.14 |
| Age, Customized < 35 years | 193 participants | 105 participants | 88 participants |
| Age, Customized ≥ 35 years | 223 participants | 102 participants | 121 participants |
| Age, Customized < 65 years | 408 participants | 202 participants | 206 participants |
| Age, Customized ≥ 65 years | 8 participants | 5 participants | 3 participants |
| Baseline Disease Activity - Categorical CDAI ≤ 330 | 280 participants | 148 participants | 132 participants |
| Baseline Disease Activity - Categorical CDAI > 330 | 136 participants | 59 participants | 77 participants |
| Baseline Disease Activity - Crohn's Disease Activity Index (CDAI) | 307.7 units on a scale STANDARD_DEVIATION 54.38 | 301.3 units on a scale STANDARD_DEVIATION 54.97 | 313.9 units on a scale STANDARD_DEVIATION 53.17 |
| Body Mass Index | 24.3 kg/m^2 STANDARD_DEVIATION 5.65 | 24.6 kg/m^2 STANDARD_DEVIATION 6.13 | 24.0 kg/m^2 STANDARD_DEVIATION 5.13 |
| Body Weight | 70.4 kg STANDARD_DEVIATION 18.5 | 71.3 kg STANDARD_DEVIATION 19.22 | 69.5 kg STANDARD_DEVIATION 17.76 |
| C-reactive Protein (CRP) | 18.8 mg/L STANDARD_DEVIATION 22.56 | 18.5 mg/L STANDARD_DEVIATION 21.98 | 19.0 mg/L STANDARD_DEVIATION 23.17 |
| CRP - Categorical > 10 mg/L | 206 participants | 105 participants | 101 participants |
| CRP - Categorical ≤ 2.87 mg/L | 87 participants | 41 participants | 46 participants |
| CRP - Categorical > 2.87 to ≤ 5 mg/L | 33 participants | 19 participants | 14 participants |
| CRP - Categorical > 5 to ≤ 10 mg/L | 90 participants | 42 participants | 48 participants |
| Disease Localization Colon only | 100 participants | 52 participants | 48 participants |
| Disease Localization Ileocolonic (both ileum and colon) | 254 participants | 126 participants | 128 participants |
| Disease Localization Ileum only | 62 participants | 29 participants | 33 participants |
| Draining Fistula at Baseline All Closed | 1 participants | 0 participants | 1 participants |
| Draining Fistula at Baseline No Fistula | 365 participants | 182 participants | 183 participants |
| Draining Fistula at Baseline Yes | 50 participants | 25 participants | 25 participants |
| Duration of Crohn's Disease - Categorical ≥ 1 to < 3 years | 53 participants | 25 participants | 28 participants |
| Duration of Crohn's Disease - Categorical < 1 year | 23 participants | 12 participants | 11 participants |
| Duration of Crohn's Disease - Categorical ≥ 3 to < 7 years | 104 participants | 52 participants | 52 participants |
| Duration of Crohn's Disease - Categorical ≥ 7 years | 236 participants | 118 participants | 118 participants |
| Duration of Crohn's Disease (CD) | 10.3 years STANDARD_DEVIATION 8.37 | 10.0 years STANDARD_DEVIATION 7.98 | 10.6 years STANDARD_DEVIATION 8.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 403 Participants | 199 Participants | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 4 Participants | 1 Participants |
| Extraintestinal Manifestations at Baseline No | 170 participants | 77 participants | 93 participants |
| Extraintestinal Manifestations at Baseline Yes | 246 participants | 130 participants | 116 participants |
| Fecal Calprotectin | 1288.0 μg/g STANDARD_DEVIATION 2134.79 | 1426.5 μg/g STANDARD_DEVIATION 2357.76 | 1148.1 μg/g STANDARD_DEVIATION 1878.58 |
| Fecal Calprotectin - Categorical > 250 to ≤ 500 μg/g | 70 participants | 35 participants | 35 participants |
| Fecal Calprotectin - Categorical ≤ 250 μg/g | 99 participants | 47 participants | 52 participants |
| Fecal Calprotectin - Categorical > 500 μg/g | 241 participants | 124 participants | 117 participants |
| Fecal Calprotectin - Categorical Missing | 6 participants | 1 participants | 5 participants |
| Geographic Region Asia/Australia/Africa | 32 participants | 14 participants | 18 participants |
| Geographic Region Central Europe | 87 participants | 46 participants | 41 participants |
| Geographic Region Eastern Europe | 25 participants | 15 participants | 10 participants |
| Geographic Region North America | 197 participants | 95 participants | 102 participants |
| Geographic Region Western/Northern Europe | 75 participants | 37 participants | 38 participants |
| History of Fistulizing Disease No | 268 participants | 130 participants | 138 participants |
| History of Fistulizing Disease Yes | 148 participants | 77 participants | 71 participants |
| History of Prior Surgery for Crohn's Disease No | 235 participants | 118 participants | 117 participants |
| History of Prior Surgery for Crohn's Disease Yes | 181 participants | 89 participants | 92 participants |
| Race/Ethnicity, Customized Asian | 18 participants | 9 participants | 9 participants |
| Race/Ethnicity, Customized Black | 9 participants | 5 participants | 4 participants |
| Race/Ethnicity, Customized Not Reported | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Other | 13 participants | 7 participants | 6 participants |
| Race/Ethnicity, Customized White | 374 participants | 186 participants | 188 participants |
| Sex: Female, Male Female | 236 Participants | 118 Participants | 118 Participants |
| Sex: Female, Male Male | 180 Participants | 89 Participants | 91 Participants |
| Smoking Status Current Smoker | 123 participants | 58 participants | 65 participants |
| Smoking Status Former Smoker | 98 participants | 47 participants | 51 participants |
| Smoking Status Never Smoked | 195 participants | 102 participants | 93 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 207 | 25 / 209 |
| serious Total, serious adverse events | 16 / 207 | 13 / 209 |
Outcome results
Primary
Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation
Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time frame: Week 6
Population: TNFα Antagonist Failure Intent-to-treat (ITT) subpopulation which consisted of all randomized participants who received any amount of blinded study drug who met the TNFα antagonist failure criterion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation | 12.1 percentage of participants |
| Vedolizumab | Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation | 15.2 percentage of participants |
Comparison: Clinical remission was tested using the Cochran-Mantel-Haenszel (CMH) chi-square test at a 5% significance level with stratification according to concomitant use of oral corticosteroids and concomitant use of immunomodulators (6-mercaptopurine \[6-MP\], azathioprine, or methotrexate) for the TNFα antagonist failure subpopulation.p-value: 0.433295% CI: [-4.5, 10.5]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was any AE, occurring at any dose and regardless of causality that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event based upon appropriate medical judgment that may have jeopardized the patient and may have required medical or surgical intervention to prevent 1 of the outcomes listed above, or any diagnosis of progressive multifocal leukoencephalopathy (PML). Relationship to study drug administration was determined by the investigator responding yes or no to the question: Is there a reasonable possibility that the AE is associated with the study drug?
Time frame: From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments.
Population: Overall Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | Serious infection adverse event | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse event resulting in study discontinuation | 8 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Drug-related serious adverse event | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Drug-related adverse event | 34 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse event resulting in discontinuation | 5 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse event | 16 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Death | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Any adverse event | 124 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Death | 0 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Drug-related adverse event | 34 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Adverse event resulting in study discontinuation | 4 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Serious adverse event | 13 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Serious infection adverse event | 2 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Drug-related serious adverse event | 1 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Serious adverse event resulting in discontinuation | 4 participants |
| Vedolizumab | Number of Participants With Adverse Events (AEs) | Any adverse event | 117 participants |
Secondary
Percentage of Participants in Clinical Remission at Week 10 in the Overall Population
Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time frame: Week 10
Population: Overall ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission at Week 10 in the Overall Population | 13.0 percentage of participants |
| Vedolizumab | Percentage of Participants in Clinical Remission at Week 10 in the Overall Population | 28.7 percentage of participants |
Secondary
Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation
Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time frame: Week 10
Population: TNFα Antagonist Failure Intent-to-treat (ITT) Subpopulation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation | 12.1 percentage of participants |
| Vedolizumab | Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation | 26.6 percentage of participants |
Secondary
Percentage of Participants in Clinical Remission at Week 6 in the Overall Population
Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time frame: Week 6
Population: Overall ITT population, consisting of all randomized participants who received any amount of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission at Week 6 in the Overall Population | 12.1 percentage of participants |
| Vedolizumab | Percentage of Participants in Clinical Remission at Week 6 in the Overall Population | 19.1 percentage of participants |
Secondary
Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation
Enhanced clinical response is defined as a ≥ 100-point decrease in CDAI score from Baseline. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percent deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response.
Time frame: Baseline and Week 6
Population: TNFα Antagonist Failure ITT Subpopulation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation | 22.3 percentage of participants |
| Vedolizumab | Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation | 39.2 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Remission in the Overall Population
Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission.
Time frame: Week 6 and Week 10
Population: Overall ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Sustained Clinical Remission in the Overall Population | 8.2 percentage of participants |
| Vedolizumab | Percentage of Participants With Sustained Clinical Remission in the Overall Population | 15.3 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population
Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission.
Time frame: Week 6 and Week 10
Population: TNFα Antagonist Failure ITT Subpopulation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population | 8.3 percentage of participants |
| Vedolizumab | Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population | 12.0 percentage of participants |