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An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02497469
Recruitment Status : Completed
First Posted : July 14, 2015
Results First Posted : October 10, 2019
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE July 10, 2015
First Posted Date  ICMJE July 14, 2015
Results First Submitted Date  ICMJE September 17, 2019
Results First Posted Date  ICMJE October 10, 2019
Last Update Posted Date October 10, 2019
Actual Study Start Date  ICMJE July 15, 2015
Actual Primary Completion Date September 26, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2019)
Percentage of Participants Who Achieved Clinical Remission [ Time Frame: Week 52 ]
Clinical remission was defined as a complete Mayo score of ≤2 points and no individual subscore >1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2015)
Percentage of Participants Achieving Clinical Remission [ Time Frame: Week 52 ]
Clinical remission is defined as a complete Mayo score of less than or equal to (<=) 2 points and no individual subscore greater than (>) 1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consists of 4 subscores: stool frequency, rectal bleeding, findings of endoscopy, and physician global assessment, each ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).
Change History Complete list of historical versions of study NCT02497469 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2019)
  • Percentage of Participants Who Achieved Mucosal Healing [ Time Frame: Week 52 ]
    Mucosal healing was defined as a Mayo score endoscopic subscore of <= 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
  • Percentage of Participants Who Used Oral Corticosteroids at Baseline Who Discontinued Corticosteroids and Were in Clinical Remission [ Time Frame: Week 52 ]
    Corticosteroid-free remission was defined as participants using oral corticosteroids at Baseline (Week 0) who had discontinued oral corticosteroids and were in clinical remission at Week 52. Clinical remission was defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2015)
  • Percentage of Participants Achieving Mucosal Healing [ Time Frame: Week 52 ]
    Mucosal healing is defined as Mayo endoscopic subscore <=1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Findings of endoscopy is a subscale of Mayo score, which ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).
  • Percentage of Participants Using Oral Corticosteroids at Baseline who Discontinue Corticosteroids and are in Clinical Remission [ Time Frame: Week 52 ]
    Corticosteroid-free remission: participants who discontinue corticosteroids and achieve clinical remission will be assessed in participants with baseline oral corticosteroid use. Clinical remission is defined as a complete Mayo score of <=2 points and no individual subscore >1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consists of 4 subscores: stool frequency, rectal bleeding, findings of endoscopy, and physician global assessment, each ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis
Official Title  ICMJE A Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
Brief Summary The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) treatment compared to adalimumab subcutaneous (SC) treatment over a 52-week treatment period.
Detailed Description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have ulcerative colitis. This study will look at the stool frequency, rectal bleeding and findings on endoscopy of people who take vedolizumab compared to those who take adalimumab.

The study will enroll approximately 658 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

  • Vedolizumab 300 mg IV
  • Adalimumab 160 mg on Day 1 followed by 80 mg on Week 2 then 40 mg every 2 weeks SC

All participants will receive 1 intravenous infusion on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. All participants will also receive 4 SC injections on Day 1 or 2 SC injections each on Days 1 and 2, followed by 2 SC injections in 1 day on Week 2 and then 1 SC injection every 2 weeks for up to Week 50. All participants will be asked to record the symptoms of ulcerative colitis in a daily diary.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 79 weeks. Participants will make approximately 11 visits to the clinic, and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Colitis, Ulcerative
Intervention  ICMJE
  • Drug: Vedolizumab
    Vedolizumab infusion
  • Drug: Adalimumab placebo
    Adalimumab placebo-matching injection
  • Drug: Adalimumab
    Adalimumab injection
  • Drug: Vedolizumab placebo
    Vedolizumab placebo-matching infusion
Study Arms  ICMJE
  • Experimental: Vedolizumab IV 300 mg
    Vedolizumab 300 milligram (mg), infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
    Interventions:
    • Drug: Vedolizumab
    • Drug: Adalimumab placebo
  • Active Comparator: Adalimumab SC 160/80/40 mg
    Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.
    Interventions:
    • Drug: Adalimumab
    • Drug: Vedolizumab placebo
Publications * Sands BE, Peyrin-Biroulet L, Loftus EV Jr, Danese S, Colombel JF, Törüner M, Jonaitis L, Abhyankar B, Chen J, Rogers R, Lirio RA, Bornstein JD, Schreiber S; VARSITY Study Group. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med. 2019 Sep 26;381(13):1215-1226. doi: 10.1056/NEJMoa1905725.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 17, 2019)
771
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2015)
658
Actual Study Completion Date  ICMJE January 18, 2019
Actual Primary Completion Date September 26, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Has a diagnosis of ulcerative colitis established at least 3 months prior to screening by clinical and endoscopic evidence and corroborated by a histopathology report.
  2. Has moderately to severely active ulcerative colitis as determined by a Mayo score of 6 to 12 with an endoscopic subscore greater than or equal to >=2 within 14 days prior to the randomization.
  3. Has evidence of ulcerative colitis proximal to the rectum (>=15 centimeter [cm] of involved colon).
  4. With extensive colitis (up to the hepatic flexure) or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during the Screening Period).
  5. The participant:

    1. Has had previous treatment with tumor necrosis factor- alpha (TNF-alpha) antagonists without documented clinical response to treatment (example, due to lack of response [primary nonresponders], loss of response, or intolerance [secondary nonresponders]), or
    2. Has previously used a TNF-alpha antagonists (except adalimumab), and discontinued its use due to reasons other than safety, or
    3. Is naïve to TNF-alpha antagonist therapy but is failing current treatment (example, corticosteroids, 5-aminosalicylate [5-ASA], or immunomodulators).

Exclusion Criteria:

  1. Clinical evidence of abdominal abscess or toxic megacolon at Screening.
  2. Has had an extensive colonic resection, subtotal or total colectomy.
  3. Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
  4. Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
  5. Has received any of the following for the treatment of underlying disease within 30 days of randomization:

    1. Non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide) other than those specifically listed in Section Permitted Medications For Treatment of UC.
    2. An approved non-biologic therapy in an investigational protocol.
  6. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half lives prior to the screening (whichever is longer).
  7. Has previously received natalizumab, efalizumab, adalimumab, AMG-181, anti-mucosal addressin cell adhesion molecule-1 antibodies, or rituximab.
  8. Has previously received vedolizumab.
  9. Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia.
  10. Evidence of an active infection during Screening.
  11. Evidence of, or treatment for, Clostridium difficile (C. difficile) or other intestinal pathogen within 28 days prior to the 1st dose of study drug.
  12. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection (* HBV immune participants, ie, being hepatitis B surface antigen [HBsAg], may participate).
  13. Has active or latent TB, regardless of treatment history.
  14. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the 1st dose of study drug.
  15. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Bosnia and Herzegovina,   Bulgaria,   Canada,   Colombia,   Croatia,   Czechia,   Denmark,   Estonia,   France,   Germany,   Hong Kong,   Hungary,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Mexico,   Netherlands,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Slovakia,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Chile,   Czech Republic,   Finland,   Norway,   South Africa,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT02497469
Other Study ID Numbers  ICMJE MLN0002-3026
U1111-1168-6713 ( Registry Identifier: WHO )
2015-000939-33 ( EudraCT Number )
NL54690.056.15 ( Registry Identifier: CCMO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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.
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Takeda
PRS Account Takeda
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP