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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Vedolizumab intravenous infusion.
Adalimumab injection for subcutaneous use.
Methotrexate oral tablets.
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
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
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.
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Digestive Health Specialists of the Southeast
Dothan, Alabama, United States
Gastro Florida
Clearwater, Florida, United States
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States
Grand Teton Research Group, PLLC
Idaho Falls, Idaho, United States
Northshore University HealthSystem
Evanston, Illinois, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Cotton O'Neil Clinical Research
Topeka, Kansas, United States
Texas Digestive Disease Consultants Baton Rouge
Baton Rouge, Louisiana, United States
Louisana Research Center, LLC
Shreveport, Louisiana, United States
Center for Digestive Health
Troy, Michigan, United States
...and 22 more locations
Time frame: Week 26
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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