Triple Combination Therapy in High Risk Crohn's Disease

ID: NCT02764762
Status: Recruiting
Phase: Phase 4
Start Date: April 18, 2017
First Submitted: May 05, 2016
Last Updated: February 23, 2018
Results: N/A
Organization: Takeda
Sponsors & Collaborators: Takeda
Location: Canada, United States
Conditions: Crohn Disease
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

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 Crohn's disease 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 Crohn's Disease. 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 patients. Participants will receive triple combination therapy which includes:

- Vedolizumab 300 mg

- Adalimumab 160/80/40 mg

- Methotrexate 15 mg

All participants will receive vedolizumab IV infusion on Weeks 0, 2, 6, 14 and 22 along with adalimumab 160 mg, SC 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 IV infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102.

This multi-center trial will be conducted in 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 18 weeks and 26 weeks (6 months) from the last dose of study drug.
Condition or disease Intervention/treatment Phase

Crohn Disease

Drug: Vedolizumab
Other Names
Entyvio MLN0002 IV
Drug: Adalimumab
Other Names
Drug: Methotrexate
Other Names
Phase 4

Tracking Information

First Submitted DateMay 05, 2016
Last Update Posted DateFebruary 23, 2018
Actual Start DateApril 18, 2017
Anticipated Completion DateApril 23, 2021
Actual Primary Completion DateApril 23, 2021
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Percentage of Participants Achieving Endoscopic Remission at Week 26 [Time Frame: Week 26]

    Endoscopic remission is defined as simple endoscopic score for Crohn's Disease (SES-CD) scale score from 0-2. The SES-CD evaluates 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 is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Percentage of Participants Achieving Endoscopic Healing at Week 26 [Time Frame: Week 26]

    Endoscopic healing is 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 evaluates 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 is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Achieving Endoscopic Response at Week 26 [Time Frame: Week 26]

    Endoscopic response is defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluates 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 is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Change From Baseline in SES-CD Score at Week 26 [Time Frame: Baseline and Week 26]

    The SES-CD evaluates 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 is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Achieving Deep Remission at Week 26 [Time Frame: Week 26]

    Deep remission is defined as Crohn's disease activity index (CDAI) score<150 and SES-CD score from 0-2. CDAI is scoring system for the assessment of Crohn's Disease 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, 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 is sum of values obtained for each segment. The SES-CD total is sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26 [Time Frame: Week 26]

    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 Crohn's Disease 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, 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 SES-CD total is sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26 [Time Frame: Weeks 10 and 26]

    Clinical remission is defined as CDAI score <150. CDAI is scoring system for the assessment of Crohn's Disease 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.

  • Percentage of Participants Achieving Clinical Response at Weeks 10 and 26 [Time Frame: Weeks 10 and 26]

    Clinical response is defined as ≥100-point decrease in CDAI score. CDAI is scoring system for the assessment of Crohn's Disease 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.

  • Change From Baseline in C-Reactive Protein (CRP) Levels at Weeks 10 and 26 [Time Frame: Baseline, Weeks 10 and 26]

    The change between the CRP levels collected at Weeks 10 and 26 relative to Baseline.

  • Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 26, 52, 78, and 102 [Time Frame: Baseline, Weeks 10, 26, 52, 78 and 102]

    The change between the fecal calprotectin concentrations collected at Weeks 10, 26, 52, 78, and 102 relative to Baseline.

  • Percentage of Participants Achieving Clinical Remission and CRP <5 mg/L at Weeks 26, 52, 78, and 102 [Time Frame: Weeks 26, 52, 78 and 102]

    Clinical remission is defined as CDAI score <150 and CRP level <5 mg/L in participants with elevated CRP level at Baseline. CDAI is scoring system for the assessment of Crohn's Disease 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.

  • 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 using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission at weeks 10, 26, and 102 will be reported. Clinical remission is defined as CDAI score <150. CDAI is scoring system for the assessment of Crohn's Disease 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.

  • Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102 [Time Frame: Weeks 52, 78 and 102]

    Clinical remission is defined as CDAI score <150. Clinical remission is defined as CDAI score <150. CDAI is scoring system for the assessment of Crohn's Disease 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.

  • Percentage of Participants Maintaining Endoscopic Remission at Week 102 [Time Frame: Week 102]

    Endoscopic remission is defined as SES-CD score 0-2. The SES-CD evaluates 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 is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Maintaining Deep Remission at Week 102 [Time Frame: Week 102]

    Deep remission is defined as CDAI score <150 and SES-CD score 0-2. Clinical remission is defined as CDAI score <150. CDAI is scoring system for the assessment of Crohn's Disease 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, 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 SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Maintaining Endoscopic Healing at Week 102 [Time Frame: Week 102]

    Endoscopic healing is 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 evaluates 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 is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants Maintaining Endoscopic Response at Week 102 [Time Frame: Week 102]

    Endoscopic response is defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluates 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 is sum of values obtained for each segment. The SES-CD total is 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 [Time Frame: 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 Crohn's Disease 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, 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 SES-CD total is sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  • Percentage of Participants With First Exacerbation of Crohn's disease (CD) [Time Frame: After 26 Weeks up to Week 128]

    First exacerbation of CD after 26 weeks is 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 μg/gm. Clinical remission is defined as CDAI score <150. CDAI is scoring system for the assessment of Crohn's Disease 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.

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleTriple Combination Therapy in High Risk Crohn's Disease
Official TitleAn 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
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 Crohn's disease 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 Crohn's Disease. 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 patients. Participants will receive triple combination therapy which includes:

- Vedolizumab 300 mg

- Adalimumab 160/80/40 mg

- Methotrexate 15 mg

All participants will receive vedolizumab IV infusion on Weeks 0, 2, 6, 14 and 22 along with adalimumab 160 mg, SC 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 IV infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102.

This multi-center trial will be conducted in 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 18 weeks and 26 weeks (6 months) from the last dose of study drug.

Study TypeInterventional
Study PhasePhase 4
Estimated Enrollment
60
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Crohn Disease
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Vedolizumab

Vedolizumab IV infusion

Other Names
Entyvio
MLN0002 IV
Drug: Adalimumab

Adalimumab SC injection

Other Names
Drug: Methotrexate

Methotrexate Tablets

Other Names
Study Groups/Cohorts
Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.

Study Arms
Experimental Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.
Drug : Vedolizumab
Vedolizumab IV infusion

Experimental Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.
Drug : Adalimumab
Adalimumab SC injection

Experimental Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.
Drug : Methotrexate
Methotrexate Tablets

Arm Intervention/Treatment
Experimental Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.
Drug : Vedolizumab
Experimental Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.
Drug : Adalimumab
Experimental Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, along 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 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.
Drug : Methotrexate

Recruitment Information

Recruitment Status:Recruiting
Enrollment60
Completion DateApril 23, 2021
Eligibility Criteria: Inclusion Criteria:
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative has signed and dated a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is male or non-pregnant, non-breast-feeding female and aged 18 to 80 years, inclusive at time of Screening.
4. Has an initial diagnosis of Crohn's disease (CD) established within 24 months prior to enrollment with involvement of the ileum and/or colon that can be assessed by ileocolonoscopy.
5. Has moderate to severely active CD during Screening defined by:
1. Crohn's disease activity index (CDAI) score ≥ 220 within 10 days prior to enrollment, AND
2. Centrally assessed simple endoscopic score for Crohn's disease (SES-CD) score ≥7 (or ≥4 if isolated ileal disease) during Screening, AND
3. Elevated biomarker of inflammation [C-reactive protein (CRP) >5 mg/L OR fecal calprotectin level >250 μg/g stool) during Screening.
6. By investigator judgement, the participant is assessed as having CD at moderate-high risk for complications. Investigator judgement may include clinical assessment, the Crohn's Disease Personalized Risk and Outcome Prediction Tool (PROSPECT), or criteria defined by the 2014 American Gastroenterology Association (AGA) CD Clinical Care Pathway.
7. May be receiving a stable therapeutic dose of conventional therapies for CD.
8. If on corticosteroids, must be on a stable dose of oral corticosteroids up to 20 mg of prednisone daily or 9 mg of budesonide daily for at least 7 days prior to enrollment.
9. If on corticosteroids, must be willing to follow a mandatory taper of prednisone or budesonide within 60 days after enrollment.
10. Must be willing to stop treatment with 5-aminosalicylate (5-ASA), antibiotics, and probiotics for luminal CD at enrollment.
11. Male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
12. Female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
13. Family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factors must be up-to-date on colorectal cancer surveillance (may be performed during Screening as standard of care).

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).
5. Had non-CD related abdominal surgery within 6 months prior to enrollment.
6. Has any prior CD-related surgery OR CD complication requiring surgery at any time (other than seton placement for perianal fistula without abscess).
7. Has a history of 2 or more non CD related small bowel resections or diagnosis of short bowel syndrome.
8. Has extensive non CD related colonic resection, ie, subtotal or total colectomy with <15 cm colon remaining.
9. Has an ileostomy, colostomy.
10. Has a history or evidence of adenomatous colonic polyps that have not been removed.
11. Has a history or evidence of colonic mucosal dysplasia.
12. Has intolerance or contraindication to undergo ileocolonoscopy.
13. Has known fixed stricture or stenosis of the intestine.
Infectious Disease
Exclusion Criteria
14. Has any identified congenital or acquired immunodeficiency [eg, common variable immunodeficiency, human immunodeficiency virus (HIV) infection].
15. Has undergone organ transplantation.
16. Has evidence of an active infection during Screening.
17. Infections requiring treatment with oral (PO) or intravenous (IV) antibiotics, antivirals, or antifungals within 28 days of enrollment.
18. Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
1. History of TB.
2. A diagnostic TB test performed during Screening that is positive, as defined by:
• A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR
3. A tuberculin skin test reaction ≥10 mm (≥5 mm in participants receiving the equivalent of >15 mg/day prednisone)
19. Has a history of listeria, histoplasmosis, coccidioidomycosis, blastomycosis, candidiasis, aspergillosis, legionella, or pneumocystosis.
20. Has a history of any bacterial, viral, and other infection due to opportunistic pathogens.
21. Has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
22. Has evidence of active Clostridium difficile infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening.
23. Has received any live vaccinations within 28 days prior to enrollment.
General
Exclusion Criteria
24. Has other inflammatory or rheumatic diseases (eg, psoriasis, rheumatoid arthritis, ankylosing spondylitis).
25. Had a surgical procedure requiring general anesthesia within 60 days prior to enrollment or is planning to undergo major surgery during the study period.
26. Is taking, has taken, or is required to take any excluded medications.
27. Has received either approved or investigational biologic or nonbiologic agents for the treatment of inflammatory bowel disease (IBD) in an investigational protocol.
28. Has had prior exposure to any tumor necrosis factor (TNF) antagonist including infliximab, certolizumab pegol, golimumab, adalimumab, or biosimilar TNF antagonist agents.
29. Has had prior exposure to vedolizumab, natalizumab, efalizumab, or rituximab.
30. Has received either approved or investigational biologic agents for the treatment of non-inflammatory bowel disease (IBD) conditions, other than localized injections (eg, intraocular injections for wet macular degeneration).
31. Has a history of hypersensitivity or allergies to methotrexate, vedolizumab, adalimumab, or their components.
32. Has a medical history that contraindicates the use of vedolizumab, adalimumab, or methotrexate as per each drug's package insert.
33. Has conditions which, in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.
34. Has a history of any lymphoma or lymphoproliferative disease.
35. Has a history of congestive heart failure (New York Heart Association class III/IV) or unstable angina.
36. Has renal insufficiency, ascites, pleural effusion, or underlying liver disease.
37. Has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.
38. Has had gastric bypass surgery.
39. Has symptoms of shortness of breath and cough and/or a diagnosis of clinically significant lung disease.
40. Has a history of malignancy, except for the following: adequately-treated nonmetastatic basal cell skin cancer; squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to Screening; and history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to Screening. Participants with a remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received; this must be discussed with the sponsor on a case-by-case basis prior to enrollment.
41. Has a history of any major neurological disorders, including stroke, central nervous system demyelinating disease, brain tumor, or neurodegenerative disease.
42. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of study drug.
43. Has a history of pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia (WBC count <3 × 10^9/L), thrombocytopenia (platelet count <100 × 10/L), or significant anemia (hemoglobin level <8 g/dL).
44. Has rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
45. Has any of the following laboratory abnormalities during the Screening period:
1. Hemoglobin level <8 g/dL.
2. WBC count <3 x 10^9/L.
3. Lymphocyte count <0.5 x 10^9/L.
4. Platelet count <100 x 10^9/L or >1200 x 10^9/L.
5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 the upper limit of normal (ULN).
6. Alkaline phosphatase >1.5 x ULN.
7. Renal dysfunction (serum creatinine concentration greater than 1.5 mg per deciliter [133 µmol per liter]) or estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m^2 at Screening Note: Retesting laboratory values during the screening interval may be considered with consultation from the Medical Monitor.
46. Has a history of high alcohol consumption (more than 7 drinks per week), a history of prior alcohol abuse within 5 years prior to enrollment, has alcoholic liver disease, has withdrawal symptoms, or a history of illicit drug use.
47. Has an active psychiatric problem that, in the investigator's opinion, may interfere with compliance with study procedures.
48. Is unable to attend all the study visits or comply with study procedures.
49. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g, spouse, parent, child, sibling) or may consent under duress.
50. Body mass index is >35.
51. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 6 months after participating in this study; or intending to donate ova during such time period.
52. If male, the participant intends to father a child or donate sperm during the course of this study or for 6 months thereafter.
GenderAll
Age18 Years to 80 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Canada
United States

Administrative Information

NCT Number:NCT02764762
Other Study ID Numbers
Vedolizumab-4006
U1111-1175-9094
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Takeda
Collaborators
Not Available
Investigators
Study Director
Medical Director Clinical Science
Takeda