Crohn's Disease
Conditions
Brief summary
The primary purpose of this study was to determine the effect of vedolizumab induction treatment on clinical response and remission at 6 weeks and to determine the effect of vedolizumab maintenance treatment on clinical remission at 52 weeks.
Detailed description
Study C13007 comprised 2 randomized, double-blind, placebo-controlled studies conducted under 1 protocol which, operationally, consisted of 2 phases. * The Induction Phase, designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and clinical remission, and * The Maintenance Phase, designed to establish the efficacy and safety of vedolizumab for the maintenance of clinical response and clinical remission. The 6-week Induction Phase contained 2 cohorts of participants: Cohort 1 participants were randomized and treated with double-blind study drug, and Cohort 2 participants were treated with open-label vedolizumab. The second cohort was enrolled to ensure that the sample size of Induction Phase responders randomized into the Maintenance Study provided sufficient power for the Maintenance Study primary efficacy analysis. These participants did not contribute to the efficacy analyses performed for the Induction Study. Participants in both cohorts were assessed for treatment response at Week 6. In the Maintenance Phase vedolizumab-treated participants from both Cohort 1 and Cohort 2 who demonstrated a clinical response were randomized in a 1:1:1 ratio to double-blind treatment with vedolizumab administered every 4 weeks (Q4W), vedolizumab administered every 8 weeks (Q8W), or placebo. Vedolizumab-treated participants who did not demonstrate response at Week 6 continued treatment with open-label vedolizumab, administered Q4W. Participants treated with double-blind placebo in the Induction Phase continued on double-blind placebo during the Maintenance Phase, regardless of treatment response during induction. The Maintenance Phase began at Week 6 and concluded with Week 52 assessments. After the Week 52 assessments, participants may have been eligible to enroll in Study C13008 (NCT00790933; Long-term Safety Study) to receive open-label vedolizumab treatment. Participants who withdrew early (prior to Week 52) due to sustained nonresponse, disease worsening, or the need for rescue medications may have been eligible to enroll in Study C13008. Participants who did not enroll into Study C13008 were to complete a final on-study safety assessment at Week 66 (or Final Safety visit 16 weeks after the last dose) in the Maintenance Phase of Study C13007.
Interventions
DRUGvedolizumab
Vedolizumab for intravenous infusion
OTHERPlacebo
Placebo intravenous infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 80 2. Diagnosis of moderately to severely active Crohn's disease (CD) 3. CD involvement of the ileum and/or colon 4. Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents, within protocol-specified parameters: 1. Immunomodulators 2. Tumor necrosis factor-alpha (TNFα) antagonists 3. Corticosteroids 5. May be receiving a therapeutic dose of conventional therapies for irritable bowel disease (IBD) defined by the protocol
Exclusion criteria
1. Evidence of abdominal abscess at the initial screening visit, other than a minimum of 10 aphthous ulcerations involving a minimum of 10 contiguous cm of intestine 2. Extensive colonic resection, subtotal or total colectomy 3. History of \>3 small bowel resections or diagnosis of short bowel syndrome 4. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine 5. Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol 6. Chronic hepatitis B or C infection 7. Active or latent tuberculosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Phase: Percentage of Participants Achieving Clinical Remission at Week 6 | 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. |
| Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6 | Baseline and Week 6 | Enhanced clinical response is defined as a CDAI score at least 100 points lower than 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; * Percentage deviation from standard weight. The total score ranges from 0 to 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response. |
| Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52 | Week 52 | Clinical remission is defined as a CDAI score ≤ 150. 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 600 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 |
|---|---|---|
| Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6 | Baseline and Week 6 | C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation. Normal concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with age. Higher levels indicate mild inflammation (10-40 mg/L) and active inflammation (40-200 mg/L). |
| Maintenance Phase: Percentage of Participants With Durable Clinical Remission | Assessed every 4 weeks from Week 6 to Week 50, and at Week 52 | Durable clinical remission is defined as CDAI score ≤ 150 points at 80% or more of study visits during the Maintenance Phase, including the Week 52 visit (11 of 13 study visits). The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving durable clinical remission |
| Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52 | Baseline and Week 52 | Enhanced clinical response is defined as a CDAI score at least 100 points lower than the Baseline value. 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 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response. |
| Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52 | Week 52 | Participants using oral corticosteroids at Baseline, who discontinued corticosteroids and were in clinical remission (CDAI score ≤ 150) at Week 52 achieved corticosteroid-free clinical remission. The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving corticosteroid-free clinical remission. |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
Participants took part in the study at 285 investigative sites worldwide from 23 December 2008 to 08 May 2012. The Induction Phase contained 2 cohorts. The eligibility criteria for both cohorts were identical. The purpose of Cohort 2 was to provide enough responders to power the Maintenance Phase primary efficacy analysis.
Pre-assignment details
In Cohort 1, eligible patients who met entry criteria were randomized to treatment with double-blind vedolizumab 300 mg or placebo in a 3:2 ratio. All Cohort 2 patients were treated with open-label vedolizumab. In the Maintenance Phase participants were assigned to treatment groups based on their Induction Phase treatment and response to therapy.
Participants by arm
| Arm | Count |
|---|---|
| Placebo In the Induction Phase participants in Cohort 1 were randomized to receive double-blind placebo intravenous infusions at Week 0 and Week 2. | 148 |
| Induction Phase: DB Vedolizumab In the Induction Phase participants in Cohort 1 were randomized to receive double-blind (DB) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2. | 220 |
| Induction Phase: OL Vedolizumab In the Induction Phase participants in Cohort 2 received open-label (OL) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2. | 747 |
| Total | 1,115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Induction Phase | Adverse Event | 7 | 9 | 24 | 0 | 0 | 0 | 0 |
| Induction Phase | Lack of Efficacy | 1 | 3 | 28 | 0 | 0 | 0 | 0 |
| Induction Phase | Lost to Follow-up | 0 | 0 | 3 | 0 | 0 | 0 | 0 |
| Induction Phase | Other | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Induction Phase | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Induction Phase | Withdrawal by Subject | 3 | 9 | 16 | 0 | 0 | 0 | 0 |
| Maintenance Phase | Adverse Event | 7 | 0 | 0 | 15 | 12 | 9 | 38 |
| Maintenance Phase | Lack of Efficacy | 79 | 0 | 0 | 64 | 58 | 48 | 177 |
| Maintenance Phase | Lost to Follow-up | 2 | 0 | 0 | 1 | 3 | 2 | 5 |
| Maintenance Phase | Other | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Maintenance Phase | Protocol Violation | 0 | 0 | 0 | 1 | 2 | 3 | 4 |
| Maintenance Phase | Withdrawal by Subject | 7 | 0 | 0 | 7 | 6 | 9 | 24 |
Baseline characteristics
| Characteristic | Induction Phase: DB Vedolizumab | Total | Placebo | Induction Phase: OL Vedolizumab |
|---|---|---|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 11.57 | 36.1 years STANDARD_DEVIATION 12.12 | 38.6 years STANDARD_DEVIATION 13.16 | 35.6 years STANDARD_DEVIATION 12.01 |
| Age, Customized < 35 years | 111 participants | 582 participants | 67 participants | 404 participants |
| Age, Customized ≥ 35 years | 109 participants | 533 participants | 81 participants | 343 participants |
| Age, Customized < 65 years | 218 participants | 1092 participants | 142 participants | 732 participants |
| Age, Customized ≥ 65 years | 2 participants | 23 participants | 6 participants | 15 participants |
| Baseline C-reactive Protein (CRP) | 24.1 mg/L STANDARD_DEVIATION 27.23 | 21.5 mg/L STANDARD_DEVIATION 27.45 | 23.6 mg/L STANDARD_DEVIATION 27.85 | 20.4 mg/L STANDARD_DEVIATION 27.4 |
| Baseline CRP - Categorical > 10 mg/L | 120 participants | 587 participants | 85 participants | 382 participants |
| Baseline CRP - Categorical ≤ 2.87 mg/L | 37 participants | 187 participants | 20 participants | 130 participants |
| Baseline CRP - Categorical > 2.87 to ≤ 5 mg/L | 25 participants | 114 participants | 14 participants | 75 participants |
| Baseline CRP - Categorical > 5 to ≤ 10 mg/L | 38 participants | 226 participants | 28 participants | 160 participants |
| Baseline CRP - Categorical Missing | 0 participants | 1 participants | 1 participants | 0 participants |
| Baseline Disease Activity - Categorical CDAI ≤ 330 | 119 participants | 618 participants | 81 participants | 418 participants |
| Baseline Disease Activity - Categorical CDAI > 330 | 100 participants | 491 participants | 66 participants | 325 participants |
| Baseline Disease Activity - Categorical Missing | 1 participants | 6 participants | 1 participants | 4 participants |
| Baseline Disease Activity - Crohn's Disease Activity Index (CDAI) | 327.3 units on a scale STANDARD_DEVIATION 70.67 | 323.6 units on a scale STANDARD_DEVIATION 69.37 | 324.6 units on a scale STANDARD_DEVIATION 78.08 | 322.2 units on a scale STANDARD_DEVIATION 67.17 |
| Baseline Extraintestinal Manifestations No | 87 participants | 419 participants | 41 participants | 291 participants |
| Baseline Extraintestinal Manifestations Yes | 133 participants | 696 participants | 107 participants | 456 participants |
| Baseline Fecal Calprotectin | 1839.9 μg/g STANDARD_DEVIATION 2624.92 | 1254.2 μg/g STANDARD_DEVIATION 1908.82 | 1421.2 μg/g STANDARD_DEVIATION 2076.11 | 1050.1 μg/g STANDARD_DEVIATION 1558.93 |
| Baseline Fecal Calprotectin - Categorical > 250 to ≤ 500 μg/g | 25 participants | 164 participants | 27 participants | 112 participants |
| Baseline Fecal Calprotectin - Categorical ≤ 250 μg/g | 51 participants | 286 participants | 34 participants | 201 participants |
| Baseline Fecal Calprotectin - Categorical > 500 μg/g | 134 participants | 621 participants | 81 participants | 406 participants |
| Baseline Fecal Calprotectin - Categorical Missing | 10 participants | 44 participants | 6 participants | 28 participants |
| Body Mass Index (BMI) | 23.1 kg/m^2 STANDARD_DEVIATION 5.62 | 23.9 kg/m^2 STANDARD_DEVIATION 5.93 | 23.7 kg/m^2 STANDARD_DEVIATION 5.77 | 24.2 kg/m^2 STANDARD_DEVIATION 6.02 |
| Body Weight | 67.1 kg STANDARD_DEVIATION 19.07 | 69.8 kg STANDARD_DEVIATION 19.42 | 68.7 kg STANDARD_DEVIATION 18.9 | 70.8 kg STANDARD_DEVIATION 19.56 |
| Disease Localization Colon only | 62 participants | 316 participants | 43 participants | 211 participants |
| Disease Localization Ileocolonic (both ileum and colon) | 121 participants | 618 participants | 84 participants | 413 participants |
| Disease Localization Ileum only | 37 participants | 181 participants | 21 participants | 123 participants |
| Draining Fistula at Baseline All Closed | 1 participants | 11 participants | 2 participants | 8 participants |
| Draining Fistula at Baseline No | 181 participants | 939 participants | 123 participants | 635 participants |
| Draining Fistula at Baseline Yes | 38 participants | 165 participants | 23 participants | 104 participants |
| Duration of Crohn's Disease - Categorical ≥ 1 to < 3 years | 48 participants | 201 participants | 27 participants | 126 participants |
| Duration of Crohn's Disease - Categorical < 1 year | 12 participants | 69 participants | 12 participants | 45 participants |
| Duration of Crohn's Disease - Categorical ≥ 3 to < 7 years | 49 participants | 285 participants | 45 participants | 191 participants |
| Duration of Crohn's Disease - Categorical ≥ 7 years | 111 participants | 560 participants | 64 participants | 385 participants |
| Duration of Crohn's Disease (CD) | 9.2 years STANDARD_DEVIATION 8.18 | 9.0 years STANDARD_DEVIATION 7.77 | 8.2 years STANDARD_DEVIATION 7.8 | 9.2 years STANDARD_DEVIATION 7.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 26 Participants | 5 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 214 Participants | 1065 Participants | 139 Participants | 712 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 24 Participants | 4 Participants | 16 Participants |
| History of Extraintestinal Manifestations No | 43 participants | 196 participants | 25 participants | 128 participants |
| History of Extraintestinal Manifestations Yes | 177 participants | 919 participants | 123 participants | 619 participants |
| History of Fistulizing Disease No | 130 participants | 705 participants | 92 participants | 483 participants |
| History of Fistulizing Disease Yes | 90 participants | 410 participants | 56 participants | 264 participants |
| History of Prior Surgery for Crohn's Disease No | 122 participants | 649 participants | 94 participants | 433 participants |
| History of Prior Surgery for Crohn's Disease Yes | 98 participants | 466 participants | 54 participants | 314 participants |
| Race/Ethnicity, Customized Asian | 35 participants | 89 participants | 19 participants | 35 participants |
| Race/Ethnicity, Customized Black | 3 participants | 23 participants | 3 participants | 17 participants |
| Race/Ethnicity, Customized Other | 0 participants | 8 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized White | 182 participants | 995 participants | 124 participants | 689 participants |
| Region of Enrollment Australia | 10 participants | 45 participants | 5 participants | 30 participants |
| Region of Enrollment Austria | 3 participants | 14 participants | 4 participants | 7 participants |
| Region of Enrollment Belgium | 17 participants | 70 participants | 12 participants | 41 participants |
| Region of Enrollment Bulgaria | 7 participants | 14 participants | 5 participants | 2 participants |
| Region of Enrollment Canada | 12 participants | 137 participants | 22 participants | 103 participants |
| Region of Enrollment Czech Republic | 16 participants | 80 participants | 11 participants | 53 participants |
| Region of Enrollment Denmark | 2 participants | 10 participants | 0 participants | 8 participants |
| Region of Enrollment Estonia | 2 participants | 6 participants | 1 participants | 3 participants |
| Region of Enrollment France | 3 participants | 44 participants | 4 participants | 37 participants |
| Region of Enrollment Germany | 1 participants | 50 participants | 0 participants | 49 participants |
| Region of Enrollment Greece | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Hong Kong | 0 participants | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Hungary | 17 participants | 73 participants | 9 participants | 47 participants |
| Region of Enrollment Iceland | 0 participants | 4 participants | 0 participants | 4 participants |
| Region of Enrollment India | 19 participants | 34 participants | 10 participants | 5 participants |
| Region of Enrollment Ireland | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Israel | 4 participants | 18 participants | 2 participants | 12 participants |
| Region of Enrollment Italy | 0 participants | 14 participants | 1 participants | 13 participants |
| Region of Enrollment Korea, Republic of | 12 participants | 26 participants | 3 participants | 11 participants |
| Region of Enrollment Latvia | 2 participants | 2 participants | 0 participants | 0 participants |
| Region of Enrollment Malaysia | 3 participants | 9 participants | 1 participants | 5 participants |
| Region of Enrollment Netherlands | 0 participants | 7 participants | 0 participants | 7 participants |
| Region of Enrollment New Zealand | 5 participants | 12 participants | 4 participants | 3 participants |
| Region of Enrollment Norway | 0 participants | 13 participants | 0 participants | 13 participants |
| Region of Enrollment Poland | 6 participants | 27 participants | 7 participants | 14 participants |
| Region of Enrollment Romania | 1 participants | 5 participants | 0 participants | 4 participants |
| Region of Enrollment Russian Federation | 9 participants | 28 participants | 4 participants | 15 participants |
| Region of Enrollment Serbia | 0 participants | 3 participants | 0 participants | 3 participants |
| Region of Enrollment Singapore | 0 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Slovakia | 5 participants | 18 participants | 3 participants | 10 participants |
| Region of Enrollment South Africa | 3 participants | 20 participants | 3 participants | 14 participants |
| Region of Enrollment Spain | 0 participants | 7 participants | 1 participants | 6 participants |
| Region of Enrollment Sweden | 1 participants | 9 participants | 0 participants | 8 participants |
| Region of Enrollment Switzerland | 1 participants | 10 participants | 0 participants | 9 participants |
| Region of Enrollment Taiwan | 0 participants | 3 participants | 0 participants | 3 participants |
| Region of Enrollment Turkey | 3 participants | 6 participants | 2 participants | 1 participants |
| Region of Enrollment Ukraine | 4 participants | 16 participants | 3 participants | 9 participants |
| Region of Enrollment United Kingdom | 0 participants | 6 participants | 0 participants | 6 participants |
| Region of Enrollment United States | 52 participants | 268 participants | 28 participants | 188 participants |
| Sex: Female, Male Female | 115 Participants | 595 Participants | 79 Participants | 401 Participants |
| Sex: Female, Male Male | 105 Participants | 520 Participants | 69 Participants | 346 Participants |
| Smoking Status Current smoker | 54 participants | 298 participants | 34 participants | 210 participants |
| Smoking Status Former smoker | 46 participants | 260 participants | 29 participants | 185 participants |
| Smoking Status Missing | 0 participants | 1 participants | 0 participants | 1 participants |
| Smoking Status Nonsmoker (never smoked) | 120 participants | 556 participants | 85 participants | 351 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 96 / 148 | 96 / 153 | 476 / 814 |
| serious Total, serious adverse events | 23 / 148 | 23 / 153 | 199 / 814 |
Outcome results
Primary
Induction Phase: Percentage of Participants Achieving Clinical Remission at 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.
Time frame: Week 6
Population: Induction Study Intention to Treat (ITT) Population, which consisted of all randomized patients in Cohort 1 who received any amount of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Induction Phase: Percentage of Participants Achieving Clinical Remission at Week 6 | 6.8 percentage of participants |
| DB Vedolizumab | Induction Phase: Percentage of Participants Achieving Clinical Remission at Week 6 | 14.5 percentage of participants |
Comparison: The Hochberg method was applied to control the overall Type I error rate at a 5% significance level for the multiple comparisons of the primary endpoints. If both p-values were ≤ 0.05, both primary endpoints were to be declared significant. If 1 of the p-values for the primary endpoints was \> 0.05, the other p-value was to be tested at the 0.025 level and declared significant only if the p-value was ≤ 0.025. If neither primary was declared significant, no further testing was to be conducted.p-value: 0.020695% CI: [1.2, 14.3]Cochran-Mantel-Haenszel
Primary
Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6
Enhanced clinical response is defined as a CDAI score at least 100 points lower than 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; * Percentage deviation from standard weight. The total score ranges from 0 to 600 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: Induction Study ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6 | 25.7 percentage of participants |
| DB Vedolizumab | Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6 | 31.4 percentage of participants |
Comparison: The Hochberg method was applied to control the overall Type I error rate at a 5% significance level for the multiple comparisons of the primary endpoints. If both p-values were ≤ 0.05, both primary endpoints were to be declared significant. If 1 of the p-values for the primary endpoints was \> 0.05, the other p-value was to be tested at the 0.025 level and declared significant only if the p-value was ≤ 0.025. If neither primary was declared significant, no further testing was to be conducted.p-value: 0.232295% CI: [-3.6, 15]Cochran-Mantel-Haenszel
Primary
Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52
Clinical remission is defined as a CDAI score ≤ 150. 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 600 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 52
Population: Maintenance Study ITT Population, defined as all randomized participants who received vedolizumab during the Induction Phase and met the protocol definition of clinical response at Week 6, as assessed by the investigator, were randomized, and received any amount of double-blind study drug in the Maintenance Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52 | 21.6 percentage of participants |
| DB Vedolizumab | Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52 | 39.0 percentage of participants |
| Vedolizumab Q4W | Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52 | 36.4 percentage of participants |
Comparison: The Hochberg method was applied to control the overall Type I error rate at a 5% significance level. If both p-values were ≤ 0.05, both dose regimens were to be declared significant. If 1 of the p-values for the 2 dose comparisons was \> 0.05, the other p-value was to be tested at the 0.025 level and declared significant only if the p-value was ≤ 0.025. If neither dose was declared significant for the primary endpoint, no further testing was to be conducted.p-value: 0.000795% CI: [7.3, 27.5]Cochran-Mantel-Haenszel
Comparison: The Hochberg method was applied to control the overall Type I error rate at a 5% significance level. If both p-values were ≤ 0.05, both dose regimens were to be declared significant. If 1 of the p-values for the 2 dose comparisons was \> 0.05, the other p-value was to be tested at the 0.025 level and declared significant only if the p-value was ≤ 0.025. If neither dose was declared significant for the primary endpoint, no further testing was to be conducted.p-value: 0.004295% CI: [4.6, 24.7]Cochran-Mantel-Haenszel
Secondary
Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6
C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation. Normal concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with age. Higher levels indicate mild inflammation (10-40 mg/L) and active inflammation (40-200 mg/L).
Time frame: Baseline and Week 6
Population: Induction Study ITT Population; last observation carried forward (LOCF) imputation was used. Baseline CRP was missing for one participant in the placebo group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6 | -0.5 mg/L |
| DB Vedolizumab | Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6 | -0.9 mg/L |
Comparison: If at least 1 of the primary endpoints was significant, the sequential Hochberg procedure was to be used to test the secondary endpoint for significance at the 0.05% level.p-value: 0.9288Wilcoxon (Mann-Whitney)
Secondary
Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52
Participants using oral corticosteroids at Baseline, who discontinued corticosteroids and were in clinical remission (CDAI score ≤ 150) at Week 52 achieved corticosteroid-free clinical remission. The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving corticosteroid-free clinical remission.
Time frame: Week 52
Population: Maintenance Study ITT Population, participants who were on corticosteroids at Baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52 | 15.9 percentage of participants |
| DB Vedolizumab | Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52 | 31.7 percentage of participants |
| Vedolizumab Q4W | Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52 | 28.8 percentage of participants |
Comparison: To maintain the overall Type I error rate at 5% in the multiple-dose comparisons in each key secondary endpoint, the Hochberg method was used. To further maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially. The first key secondary endpoint was tested only if 1 or both of the primary comparisons were significant and the next key secondary endpoint was to be tested only if the previous key secondary endpoint was significant for at least 1 dose.p-value: 0.015495% CI: [3, 28.7]Cochran-Mantel-Haenszel
Comparison: To maintain the overall Type I error rate at 5% in the multiple-dose comparisons in each key secondary endpoint, the Hochberg method was used. To further maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially. The first key secondary endpoint was tested only if 1 or both of the primary comparisons were significant and the next key secondary endpoint was to be tested only if the previous key secondary endpoint was significant for at least 1 dose.p-value: 0.04595% CI: [0.3, 25.5]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Durable Clinical Remission
Durable clinical remission is defined as CDAI score ≤ 150 points at 80% or more of study visits during the Maintenance Phase, including the Week 52 visit (11 of 13 study visits). The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving durable clinical remission
Time frame: Assessed every 4 weeks from Week 6 to Week 50, and at Week 52
Population: Maintenance Study ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Maintenance Phase: Percentage of Participants With Durable Clinical Remission | 14.4 percentage of participants |
| DB Vedolizumab | Maintenance Phase: Percentage of Participants With Durable Clinical Remission | 21.4 percentage of participants |
| Vedolizumab Q4W | Maintenance Phase: Percentage of Participants With Durable Clinical Remission | 16.2 percentage of participants |
Comparison: To maintain the overall Type I error rate at 5% in the multiple-dose comparisons in each key secondary endpoint, the Hochberg method was used. To further maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially. The first key secondary endpoint was tested only if 1 or both of the primary comparisons were significant and the next key secondary endpoint was to be tested only if the previous key secondary endpoint was significant for at least 1 dose.p-value: 0.103695% CI: [-1.5, 16]Cochran-Mantel-Haenszel
Comparison: To maintain the overall Type I error rate at 5% in the multiple-dose comparisons in each key secondary endpoint, the Hochberg method was used. To further maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially. The first key secondary endpoint was tested only if 1 or both of the primary comparisons were significant and the next key secondary endpoint was to be tested only if the previous key secondary endpoint was significant for at least 1 dose.p-value: 0.641395% CI: [-6.3, 10.2]Cochran-Mantel-Haenszel
Secondary
Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52
Enhanced clinical response is defined as a CDAI score at least 100 points lower than the Baseline value. 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 600 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 52
Population: Maintenance Study ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52 | 30.1 percentage of participants |
| DB Vedolizumab | Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52 | 43.5 percentage of participants |
| Vedolizumab Q4W | Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52 | 45.5 percentage of participants |
Comparison: To maintain the overall Type I error rate at 5% in the multiple-dose comparisons in each key secondary endpoint, the Hochberg method was used. To further maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially. The first key secondary endpoint was tested only if 1 or both of the primary comparisons were significant and the next key secondary endpoint was to be tested only if the previous key secondary endpoint was significant for at least 1 dose.p-value: 0.013295% CI: [2.8, 24]Cochran-Mantel-Haenszel
Comparison: To maintain the overall Type I error rate at 5% in the multiple-dose comparisons in each key secondary endpoint, the Hochberg method was used. To further maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially. The first key secondary endpoint was tested only if 1 or both of the primary comparisons were significant and the next key secondary endpoint was to be tested only if the previous key secondary endpoint was significant for at least 1 dose.p-value: 0.005395% CI: [4.6, 26]Cochran-Mantel-Haenszel