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

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ClinicalTrials.gov Identifier: NCT02764762
Recruitment Status : Recruiting
First Posted : May 6, 2016
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to determine the effect of triple combination therapy with an anti-integrin (vedolizumab intravenous [IV]), a tumor necrosis factor (TNF) antagonist (adalimumab subcutaneously [SC]), and an immunomodulator (oral methotrexate) on endoscopic remission in participants with newly-diagnosed CD stratified at higher risk for complications.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Vedolizumab Drug: Adalimumab Drug: Methotrexate Phase 4

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 12, 2017
Estimated Primary Completion Date : May 23, 2019
Estimated Study Completion Date : April 23, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Vedolizumab 300 mg+Adalimumab 160-40 mg+Methotrexate 15 mg
In Triple Combination Therapy Phase, vedolizumab 300 milligram (mg), intravenous infusion, once at Weeks 0, 2, 6, 14 and 22, along with adalimumab 160 mg subcutaneously, 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 intravenous infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102.
Drug: Vedolizumab
Vedolizumab intravenous infusion.
Other Names:
  • Entyvio
  • MLN0002 IV

Drug: Adalimumab
Adalimumab injection for subcutaneous use.
Other Name: Humira

Drug: Methotrexate
Methotrexate oral tablets.




Primary Outcome Measures :
  1. 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, 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 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.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving Endoscopic Healing at Week 26 [ Time Frame: Week 26 ]
    Endoscopic healing is defined as SES-CD score less than or equal to (<=) 4 and reduction from Baseline in SES-CD score of at least 2 points and no individual SES-CD subscore greater than (>) 1. 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 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.

  2. 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, 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 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.

  3. 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, 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 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.

  4. 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 less than (<) 150 and SES-CD score from 0-2. CDAI is 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 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 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.

  5. 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 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.

  6. 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 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.

  7. Percentage of Participants Achieving Clinical Response at Weeks 10 and 26 [ Time Frame: Weeks 10 and 26 ]
    Clinical response is defined as greater than or equal to (>=) 100-point decrease in CDAI score. CDAI is 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 are seen with extremely severe disease.

  8. 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.

  9. 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 ]
    The change between the fecal calprotectin concentrations collected at Weeks 10, 14, 26, 52, 78, and 102 relative to Baseline.

  10. 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 ]
    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 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.

  11. 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 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.

  12. 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 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.

  13. 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, 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 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.

  14. 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 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 the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  15. 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, 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 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.

  16. 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, 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 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.

  17. 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 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.

  18. Percentage of Participants with First Exacerbation of 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 microgram per gram (mcg/g) alone. Clinical remission is defined as CDAI score <150. CDAI is 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 are seen with extremely severe disease.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02764762


Contacts
Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

  Show 32 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Clinical Science Takeda

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02764762     History of Changes
Other Study ID Numbers: Vedolizumab-4006
U1111-1175-9094 ( Registry Identifier: WHO )
First Posted: May 6, 2016    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Methotrexate
Adalimumab
Vedolizumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents
Gastrointestinal Agents