Crohn DiseasePhase 4NCT02764762
Triple Combination Therapy in High Risk Crohn's Disease (CD)
A Phase 4 study testing Vedolizumab, Adalimumab and Methotrexate in people with Crohn Disease, run by Takeda at 32 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Vedolizumab, Adalimumab and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 32 sitesin 2 countries
- Study dates
- 18 Apr 2017to 5 Jul 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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).
Who cannot join
- Gastrointestinal (GI) Exclusion Criteria
- Has a diagnosis of ulcerative colitis (UC) or indeterminate colitis.
- Has clinical evidence of a current abdominal abscess or a history of prior abdominal abscess.
- Has a known perianal fistula with abscess. (The participant may have a perianal fistula without abscess.)
- Has a known fistula (other than perianal fistula).
Trial locations and contacts
32 sites in 2 countries.
32 sites in 2 countries
United States27 sites
Digestive Health Partners, PS
Asheville, North Carolina, 28801
Atlanta Gastroenterology Associates
Atlanta, Georgia, 30342-5000
Texas Digestive Disease Consultants Baton Rouge
Baton Rouge, Louisiana, 70809
Carolinas HealthCare System Digestive Health
Charlotte, North Carolina, 28204
Gastro Florida
Clearwater, Florida, 33761
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Digestive Health Specialists of the Southeast
Dothan, Alabama, 36305
Northshore University HealthSystem
Evanston, Illinois, 60201
Baylor College of Medicine
Houston, Texas, 77030
Grand Teton Research Group, PLLC
Idaho Falls, Idaho, 83404
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Kansas Medical Center
Kansas City, Kansas, 66160
Las Vegas Medical Research
Las Vegas, Nevada, 89113
Icahn School of Medicine at Mt. Sinai
New York, New York, 10029
Digestive Disease Specialists, Inc.
Oklahoma City, Oklahoma, 73112
Minnesota Gastroenterology, PA - Plymouth
Plymouth, Minnesota, 55446
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132
Pinnacle Clinical Research
San Antonio, Texas, 78229
Louisana Research Center, LLC
Shreveport, Louisiana, 71105
Texas Digestive Disease Consultants Southlake
Southlake, Texas, 76092
Digestive Health Specialists
Tacoma, Washington, 98405
Cotton O'Neil Clinical Research
Topeka, Kansas, 66606
Center for Digestive Health
Troy, Michigan, 48098
Options Health Research, LLC
Tulsa, Oklahoma, 74104
Tyler Research Institute, LLC
Tyler, Texas, 75701
Texas Digestive Disease Consultants, Webster
Webster, Texas, 77598
Huron Gastroenterology Associates
Ypsilanti, Michigan, 48197
Canada5 sites
Covenant Health
Edmonton, Alberta, T6L 6K3
LHSC - Victoria Hospital
London, Ontario, N6A 5W9
CIUSSS de I'Estrie-CHUS
Sherbrooke, Quebec, J1G 2E8
Toronto Digestive Disease Associates Inc
Vaughan, Ontario, L4L 4Y7
PerCuro Clinical Research Ltd
Victoria, British Columbia, V8V 3M9
About this study
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
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.
Read the 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.
- Conditions
- Crohn Disease
- Being tested
- Vedolizumab, Adalimumab, Methotrexate
- Keywords
- Drug Therapy
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VedolizumabDrug
Also called Entyvio, MLN0002 IV
Vedolizumab intravenous infusion.
AdalimumabDrug
Also called Humira
Adalimumab injection for subcutaneous use.
MethotrexateDrug
Methotrexate oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Experimental | In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, with adalimumab 160 mg subcutaneously (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. In Monotherapy Phase, vedolizumab 300 mg IV infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102. Receives: Drug: Vedolizumab; Drug: Adalimumab; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 26
Secondary outcomes (19)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: After 26 Weeks up to Week 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study start18 Apr 2017
- Primary completion22 Sep 2020
- Study completion5 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02764762
- Sponsor's protocol ID
- Vedolizumab-4006
- Other IDs
- U1111-1175-9094
- Status last verified
- Jun 2023
- First submitted
- 5 May 2016
- Last updated
- 14 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Colombel JF, Ungaro RC, Sands BE, Siegel CA, Wolf DC, Valentine JF, Feagan BG, Neustifter B, Kadali H, Nazarey P, James A, Jairath V, Qasim Khan RM. Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER). Clin Gastroenterol Hepatol. 2024 Jul;22(7):1487-1496.e12. doi: 10.1016/j.cgh.2023.09.010. Epub 2023 Sep 22.
PubMed 37743037
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02764762
- Acronym / sponsor ID
- Vedolizumab-4006
- Conditions
- Crohn Disease
- Keywords
- Drug Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 22 Sep 2020 (actual)
- Study completion
- 5 Jul 2022 (actual)
- First posted
- 6 May 2016 (estimated)
- Results
- Posted 21 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) | Experimental | Drug: Vedolizumab, Drug: Adalimumab, Drug: MethotrexateIn Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, with adalimumab 160 mg subcutaneously (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. In Monotherapy Phase, vedolizumab 300 mg IV infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
- 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).
Key exclusion criteria (5 listed)
- Gastrointestinal (GI) Exclusion Criteria
- Has a diagnosis of ulcerative colitis (UC) or indeterminate colitis.
- Has clinical evidence of a current abdominal abscess or a history of prior abdominal abscess.
- Has a known perianal fistula with abscess. (The participant may have a perianal fistula without abscess.)
- Has a known fistula (other than perianal fistula).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VedolizumabAlso: Entyvio, MLN0002 IVVedolizumab intravenous infusion. | Drug | Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) |
| AdalimumabAlso: HumiraAdalimumab injection for subcutaneous use. | Drug | Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) |
| MethotrexateMethotrexate oral tablets. | Drug | Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral) |
Primary outcome
Percentage of Participants Achieving Endoscopic Remission at Week 26
Time frame: 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.
19 secondary outcomes
Percentage of Participants Achieving Endoscopic Healing at Week 26
Time frame: Week 26
Percentage of Participants Achieving Endoscopic Response at Week 26
Time frame: Week 26
Change From Baseline in SES-CD Score at Week 26
Time frame: Baseline and Week 26
Percentage of Participants Achieving Deep Remission at Week 26
Time frame: Week 26
Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26
Time frame: Week 26
Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26
Time frame: Weeks 10 and 26
Percentage of Participants Achieving Clinical Response at Weeks 10 and 26
Time frame: Weeks 10 and 26
Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26
Time frame: Baseline, Weeks 10 and 26
Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102
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
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
Time frame: Weeks 10, 26 and 102
Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102
Time frame: Weeks 52, 78 and 102
Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102
Time frame: Weeks 52, 78 and 102
Percentage of Participants Maintaining Endoscopic Remission at Week 102
Time frame: Week 102
Percentage of Participants Maintaining Deep Remission at Week 102
Time frame: Week 102
Percentage of Participants Maintaining Endoscopic Healing at Week 102
Time frame: Week 102
Percentage of Participants Maintaining Endoscopic Response at Week 102
Time frame: Week 102
Percentage of Participants Maintaining Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 102
Time frame: Week 102
Percentage of Participants With First Exacerbation of CD
Time frame: After 26 Weeks up to Week 120
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37743037Colombel JF, Ungaro RC, Sands BE, Siegel CA, Wolf DC, Valentine JF, Feagan BG, Neustifter B, Kadali H, Nazarey P, James A, Jairath V, Qasim Khan RM. Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER). Clin Gastroenterol Hepatol. 2024 Jul;22(7):1487-1496.e12. doi: 10.1016/j.cgh.2023.09.010. Epub 2023 Sep 22.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
32 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vedolizumab, Adalimumab and Methotrexate in people with Crohn Disease, run by Takeda at 32 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Endoscopic Remission at Week 26 (time frame: Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02764762, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2023.