Triple Combination Therapy in High Risk Crohn's Disease (CD)

Crohn Disease Clinical Trial

Official title:

An Open-Label, Phase 4 Study to Evaluate the Efficacy and Safety of Triple Combination Therapy With Vedolizumab IV, Adalimumab SC, and Oral Methotrexate in Early Treatment of Subjects With Crohn's Disease Stratified at Higher Risk for Developing Complications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02764762
• Other study ID #: Vedolizumab-4006
• Secondary ID: U1111-1175-9094
• Status: Completed
• Phase: Phase 4
• Start date: April 18, 2017
• Est. completion date: July 5, 2022

Study information

• Verified date: June 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: July 5, 2022
• Est. primary completion date: September 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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) Exclusion Criteria

1. Has a diagnosis of ulcerative colitis (UC) or indeterminate colitis.

2. Has clinical evidence of a current abdominal abscess or a history of prior abdominal abscess.

3. Has a known perianal fistula with abscess. (The participant may have a perianal fistula without abscess.)

4. Has a known fistula (other than perianal fistula).

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Vedolizumab
Vedolizumab intravenous infusion.
• Adalimumab
Adalimumab injection for subcutaneous use.
• Methotrexate
Methotrexate oral tablets.

Locations

Country	Name	City	State
Canada	Covenant Health	Edmonton	Alberta
Canada	LHSC - Victoria Hospital	London	Ontario
Canada	CIUSSS de I'Estrie-CHUS	Sherbrooke	Quebec
Canada	Toronto Digestive Disease Associates Inc	Vaughan	Ontario
Canada	PerCuro Clinical Research Ltd	Victoria	British Columbia
United States	Digestive Health Partners, PS	Asheville	North Carolina
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Texas Digestive Disease Consultants Baton Rouge	Baton Rouge	Louisiana
United States	Carolinas HealthCare System Digestive Health	Charlotte	North Carolina
United States	Gastro Florida	Clearwater	Florida
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Northshore University HealthSystem	Evanston	Illinois
United States	Baylor College of Medicine	Houston	Texas
United States	Grand Teton Research Group, PLLC	Idaho Falls	Idaho
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	Digestive Disease Specialists, Inc.	Oklahoma City	Oklahoma
United States	Minnesota Gastroenterology, PA - Plymouth	Plymouth	Minnesota
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Pinnacle Clinical Research	San Antonio	Texas
United States	Louisana Research Center, LLC	Shreveport	Louisiana
United States	Texas Digestive Disease Consultants Southlake	Southlake	Texas
United States	Digestive Health Specialists	Tacoma	Washington
United States	Cotton O'Neil Clinical Research	Topeka	Kansas
United States	Center for Digestive Health	Troy	Michigan
United States	Options Health Research, LLC	Tulsa	Oklahoma
United States	Tyler Research Institute, LLC	Tyler	Texas
United States	Texas Digestive Disease Consultants, Webster	Webster	Texas
United States	Huron Gastroenterology Associates	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Week 26
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.	Week 26
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.	Week 26
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.	Baseline and Week 26
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.	Week 26
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.	Week 26
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.	Weeks 10 and 26
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.	Weeks 10 and 26
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.	Baseline, Weeks 10 and 26
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.	Baseline, Weeks 10, 14, 26, 52, 78 and 102
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.	Weeks 26, 52, 78 and 102
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.	Weeks 10, 26 and 102
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.	Weeks 52, 78 and 102
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.	Weeks 52, 78 and 102
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.	Week 102
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.	Week 102
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.	Week 102
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.	Week 102
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.	Week 102
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.	After 26 Weeks up to Week 120