Crohn Disease
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to determine the effect of triple combination therapy with an anti-integrin (vedolizumab intravenous \[IV\]), a tumor necrosis factor (TNF) antagonist (adalimumab subcutaneously \[SC\]), and an immunomodulator (oral methotrexate) on endoscopic remission in participants with newly-diagnosed CD stratified at higher risk for complications.
Detailed description
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have CD. This study will look at the endoscopic remission and mucosal healing of gastrointestinal tract of people who take vedolizumab as triple combination therapy with adalimumab and methotrexate. The study will enroll approximately 60 participants. Participants will receive triple combination therapy which includes: * Vedolizumab 300 mg (intravenous) * Adalimumab 160/80/40 mg (subcutaneous) * Methotrexate 15 mg (oral) All participants will receive vedolizumab intravenous infusion on Weeks 0, 2, 6, 14 and 22 along with adalimumab 160 mg, subcutaneous injection at Week 0, 80 mg at Week 2, then 40 mg once at Week 4 and every 2 weeks thereafter until Week 26 along with methotrexate tablets orally, once weekly from Weeks 0 up to Week 34. In monotherapy phase, all participants will receive vedolizumab intravenous infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102. This multi-center trial will be conducted in the United States and Canada. The overall time to participate in this study is 128 weeks. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a safety follow-up assessment. Participants will also participate in a long-term safety questionnaire, by phone, at 26 weeks (6 months) from the last dose of study drug.
Interventions
DRUGVedolizumab
Vedolizumab intravenous infusion.
DRUGAdalimumab
Adalimumab injection for subcutaneous use.
DRUGMethotrexate
Methotrexate oral tablets.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Has an initial diagnosis of CD established within 24 months prior to screening with involvement of the ileum and/or colon that can be assessed by ileocolonoscopy. 2. Has moderate to severely active CD during Screening defined by a centrally assessed simple endoscopic score for Crohn disease (SES-CD) score \>=7 (or \>=4 if isolated ileal disease).
Exclusion criteria
Gastrointestinal (GI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Endoscopic Remission at Week 26 | Week 26 | Endoscopic remission was defined as simple endoscopic score for Crohn's Disease (SES-CD) scale score from 0-2. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that was ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Endoscopic Response at Week 26 | Week 26 | Endoscopic response was defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal. |
| Change From Baseline in SES-CD Score at Week 26 | Baseline and Week 26 | The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Negative change indicates improvement. |
| Percentage of Participants Achieving Deep Remission at Week 26 | Week 26 | Deep remission was defined as Crohn's disease activity index (CDAI) score \<150 and SES-CD score from 0-2. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26 | Week 26 | Clinical remission was defined as CDAI score \<150. Endoscopic response was defined as 50% reduction in SES-CD score from Baseline, as mucosal healing. CDAI was scoring system for assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The SES-CD total was sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26 | Weeks 10 and 26 | Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Achieving Clinical Response at Weeks 10 and 26 | Weeks 10 and 26 | Clinical response was defined as ≥100-point decrease in CDAI score. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal. |
| Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26 | Baseline, Weeks 10 and 26 | The change between the CRP levels were collected at Weeks 10 and 26 relative to Baseline. Negative change indicates improvement. |
| Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Baseline, Weeks 10, 14, 26, 52, 78 and 102 | The change between the fecal calprotectin concentrations collected at Weeks 10, 14, 26, 52, 78, and 102 relative to Baseline were reported. Baseline is defined as the last observation prior to the first dose of the study drug. |
| Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102 | Weeks 26, 52, 78 and 102 | Clinical remission was defined as CDAI score \<150 and CRP level \<5 mg/L in participants with elevated CRP level at Baseline. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicate active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Achieving Endoscopic Healing at Week 26 | Week 26 | Endoscopic healing was defined as SES-CD score ≤4 and reduction from Baseline in SES-CD score of at least 2 points and no individual SES-CD subscore \>1. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102 | Weeks 52, 78 and 102 | Clinical remission was defined as CDAI score \<150. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102 | Weeks 52, 78 and 102 | Clinical response was defined as ≥100-point decrease in CDAI score. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Maintaining Endoscopic Remission at Week 102 | Week 102 | Endoscopic remission was defined as SES-CD score 0-2. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicated more severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Maintaining Deep Remission at Week 102 | Week 102 | Deep remission was defined as CDAI score \<150 and SES-CD score 0-2. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Maintaining Endoscopic Healing at Week 102 | Week 102 | Endoscopic healing was defined as SES-CD score \<=4 and reduction from Baseline in SES-CD score of at least 2 points and no individual SES-CD subscore \>1. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal. |
| Percentage of Participants Maintaining Endoscopic Response at Week 102 | Week 102 | Endoscopic response was defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. |
| Percentage of Participants Maintaining Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 102 | Week 102 | Clinical remission is defined as CDAI score \<150. Endoscopic response defined as 50% reduction in SES-CD score from Baseline, as mucosal healing. CDAI is scoring system for assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicate active disease and values above 450 are seen with extremely severe disease. The SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The SES-CD total is sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to the nearest decimal value. |
| Percentage of Participants With First Exacerbation of CD | After 26 Weeks up to Week 120 | First exacerbation of CD after 26 weeks was defined as either: 1) a CDAI increase of \>70 from the prior visit on 2 occasions separated by a 2-week interval, objective evidence of disease activity by colonoscopy or CRP above normal OR 2) fecal calprotectin \>250 microgram per gram (mcg/g) alone. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 are seen with extremely severe disease. Percentages are rounded off to the nearest decimal value. |
| Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102 | Weeks 10, 26 and 102 | Percentage of participants using oral corticosteroids at Baseline who had discontinued corticosteroids and were in clinical remission at weeks 10, 26, and 102 were reported. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicate active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants took part in the study at 23 investigative sites in Canada and United States from 18 April 2017 to 05 July 2022.
Pre-assignment details
Participants with newly-diagnosed Crohn's Disease (CD) with higher risk for complications were enrolled into triple combination therapy to assess efficacy and safety of vedolizumab 300 mg, adalimumab 160/80/40 mg, and methotrexate 15 mg, following monotherapy of vedolizumab 300 mg.
Participants by arm
| Arm | Count |
|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15mg (Oral) Participants received triple combination therapy of vedolizumab 300 mg, IV infusion, once at Weeks 0, 2, 6, 14 and 22, with adalimumab 160 mg SC, once at Week 0, then 80 mg once at Week 2, then 40 mg once at Week 4 and every 2 weeks thereafter until Week 26 along with oral Methotrexate 15 mg tablets orally once weekly from Weeks 0 up to Week 34. Following the triple combination treatment participants received monotherapy of vedolizumab 300 mg IV infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 16 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Pretreatment Event/Adverse Event | 9 |
| Overall Study | Reason not Specified | 1 |
| Overall Study | Site Termination | 1 |
| Overall Study | Voluntary Withdrawal | 8 |
Baseline characteristics
| Characteristic | Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15mg (Oral) |
|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 12.38 |
| Body Mass Index (BMI) | 24.26 kg/m^2 STANDARD_DEVIATION 5.029 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Height | 171.4 cm STANDARD_DEVIATION 9.55 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment Canada | 14 Participants |
| Region of Enrollment United States | 41 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 31 Participants |
| Weight | 71.87 kg STANDARD_DEVIATION 18.373 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 45 | 0 / 53 |
| other Total, other adverse events | 36 / 55 | 31 / 45 | 4 / 53 |
| serious Total, serious adverse events | 6 / 55 | 1 / 45 | 2 / 53 |
Outcome results
Primary
Percentage of Participants Achieving Endoscopic Remission at Week 26
Endoscopic remission was defined as simple endoscopic score for Crohn's Disease (SES-CD) scale score from 0-2. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that was ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.
Time frame: Week 26
Population: Full Analysis Set (FAS) included all participants who received at least 1 dose of study medication and have a post-enrollment efficacy assessment. As pre-specified in the protocol, this outcome measure reports data only in the Triple Combination Therapy Phase at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Endoscopic Remission at Week 26 | 34.5 percentage of participants |
Secondary
Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26
The change between the CRP levels were collected at Weeks 10 and 26 relative to Baseline. Negative change indicates improvement.
Time frame: Baseline, Weeks 10 and 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26 | Baseline | 7.60 milligrams per liter (mg/L) |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26 | Change From Baseline at Week 10 | -4.80 milligrams per liter (mg/L) |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26 | Change From Baseline at Week 26 | -5.50 milligrams per liter (mg/L) |
Secondary
Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102
The change between the fecal calprotectin concentrations collected at Weeks 10, 14, 26, 52, 78, and 102 relative to Baseline were reported. Baseline is defined as the last observation prior to the first dose of the study drug.
Time frame: Baseline, Weeks 10, 14, 26, 52, 78 and 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Change From Baseline at Week 14 | -556.0 micrograms per gram |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Change From Baseline at Week 26 | -860.5 micrograms per gram |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Baseline | 1301.0 micrograms per gram |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Change From Baseline at Week 10 | -864.0 micrograms per gram |
| Vedolizumab 300 mg (IV) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Change From Baseline at Week 78 | -396.5 micrograms per gram |
| Vedolizumab 300 mg (IV) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Baseline | 1210.0 micrograms per gram |
| Vedolizumab 300 mg (IV) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Change From Baseline at Week 52 | -350.0 micrograms per gram |
| Vedolizumab 300 mg (IV) | Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 | Change From Baseline at Week 102 | -452.0 micrograms per gram |
Secondary
Change From Baseline in SES-CD Score at Week 26
The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Negative change indicates improvement.
Time frame: Baseline and Week 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in SES-CD Score at Week 26 | Baseline | 12.6 score on a scale | Standard Deviation 5.67 |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Change From Baseline in SES-CD Score at Week 26 | Change From Baseline at Week 26 | -8.9 score on a scale | Standard Deviation 7.29 |
Secondary
Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102
Clinical remission was defined as CDAI score \<150 and CRP level \<5 mg/L in participants with elevated CRP level at Baseline. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicate active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.
Time frame: Weeks 26, 52, 78 and 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with Elevated CRP at Baseline. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102 | Week 26 | 51.3 percentage of participants |
| Vedolizumab 300 mg (IV) | Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102 | Week 52 | 44.1 percentage of participants |
| Vedolizumab 300 mg (IV) | Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102 | Week 78 | 26.5 percentage of participants |
| Vedolizumab 300 mg (IV) | Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102 | Week 102 | 20.6 percentage of participants |
Secondary
Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26
Clinical remission was defined as CDAI score \<150. Endoscopic response was defined as 50% reduction in SES-CD score from Baseline, as mucosal healing. CDAI was scoring system for assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The SES-CD total was sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26 | 38.2 percentage of participants |
Secondary
Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26
Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.
Time frame: Weeks 10 and 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26 | Week 10 | 60.0 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26 | Week 26 | 54.5 percentage of participants |
Secondary
Percentage of Participants Achieving Clinical Response at Weeks 10 and 26
Clinical response was defined as ≥100-point decrease in CDAI score. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.
Time frame: Weeks 10 and 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Clinical Response at Weeks 10 and 26 | Week 10 | 49.1 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Clinical Response at Weeks 10 and 26 | Week 26 | 43.6 percentage of participants |
Secondary
Percentage of Participants Achieving Deep Remission at Week 26
Deep remission was defined as Crohn's disease activity index (CDAI) score \<150 and SES-CD score from 0-2. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Deep Remission at Week 26 | 21.8 percentage of participants |
Secondary
Percentage of Participants Achieving Endoscopic Healing at Week 26
Endoscopic healing was defined as SES-CD score ≤4 and reduction from Baseline in SES-CD score of at least 2 points and no individual SES-CD subscore \>1. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Endoscopic Healing at Week 26 | 43.6 percentage of participants |
Secondary
Percentage of Participants Achieving Endoscopic Response at Week 26
Endoscopic response was defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 26
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Achieving Endoscopic Response at Week 26 | 56.4 percentage of participants |
Secondary
Percentage of Participants Maintaining Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 102
Clinical remission is defined as CDAI score \<150. Endoscopic response defined as 50% reduction in SES-CD score from Baseline, as mucosal healing. CDAI is scoring system for assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicate active disease and values above 450 are seen with extremely severe disease. The SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The SES-CD total is sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to the nearest decimal value.
Time frame: Week 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with clinical remission and endoscopic response at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 102 | 19.0 percentage of participants |
Secondary
Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102
Clinical remission was defined as CDAI score \<150. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.
Time frame: Weeks 52, 78 and 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with clinical remission at Week 26.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102 | Week 52 | 50.0 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102 | Week 78 | 33.3 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102 | Week 102 | 20.0 percentage of participants |
Secondary
Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102
Clinical response was defined as ≥100-point decrease in CDAI score. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.
Time frame: Weeks 52, 78 and 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with clinical response at Week 26.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102 | Week 52 | 66.7 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102 | Week 78 | 45.8 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102 | Week 102 | 29.2 percentage of participants |
Secondary
Percentage of Participants Maintaining Deep Remission at Week 102
Deep remission was defined as CDAI score \<150 and SES-CD score 0-2. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with deep remission at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Deep Remission at Week 102 | 8.3 percentage of participants |
Secondary
Percentage of Participants Maintaining Endoscopic Healing at Week 102
Endoscopic healing was defined as SES-CD score \<=4 and reduction from Baseline in SES-CD score of at least 2 points and no individual SES-CD subscore \>1. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with endoscopic healing at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Endoscopic Healing at Week 102 | 34.8 percentage of participants |
Secondary
Percentage of Participants Maintaining Endoscopic Remission at Week 102
Endoscopic remission was defined as SES-CD score 0-2. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicated more severe disease. Percentages are rounded off to single decimal.
Time frame: Week 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with endoscopic remission at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Endoscopic Remission at Week 102 | 27.8 percentage of participants |
Secondary
Percentage of Participants Maintaining Endoscopic Response at Week 102
Endoscopic response was defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.
Time frame: Week 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with endoscopic response at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Maintaining Endoscopic Response at Week 102 | 50.0 percentage of participants |
Secondary
Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102
Percentage of participants using oral corticosteroids at Baseline who had discontinued corticosteroids and were in clinical remission at weeks 10, 26, and 102 were reported. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicate active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.
Time frame: Weeks 10, 26 and 102
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with Baseline concomitant oral corticosteroid use. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102 | Week 10 | 50.0 percentage of participants |
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102 | Week 26 | 56.3 percentage of participants |
| Vedolizumab 300 mg (IV) | Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102 | Week 102 | 21.4 percentage of participants |
Secondary
Percentage of Participants With First Exacerbation of CD
First exacerbation of CD after 26 weeks was defined as either: 1) a CDAI increase of \>70 from the prior visit on 2 occasions separated by a 2-week interval, objective evidence of disease activity by colonoscopy or CRP above normal OR 2) fecal calprotectin \>250 microgram per gram (mcg/g) alone. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 are seen with extremely severe disease. Percentages are rounded off to the nearest decimal value.
Time frame: After 26 Weeks up to Week 120
Population: FAS included all participants who received at least 1 dose of study medication and had a post-enrollment efficacy assessment. Overall number of participants analyzed are the number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Percentage of Participants With First Exacerbation of CD | 62.2 percentage of participants |