Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis

Last updated: July 20, 2023
Sponsor: Takeda
Overall Status: Completed

Phase

4

Condition

Crohn's Disease

Inflammatory Bowel Disease

Treatment

Vedolizumab IV

Clinical Study ID

NCT03029143
Vedolizumab-4014
U1111-1183-0451
  • Ages 18-85
  • All Genders

Study Summary

The purpose of this study is to investigate the efficacy and safety of vedolizumab intravenous (IV) dose optimization on mucosal healing compared with the standard vedolizumab IV dosing regimen over a 30 week treatment period in participants with moderately to severely active ulcerative colitis (UC) and high vedolizumab clearance, based on a Week 5 predefined serum vedolizumab concentration threshold less than (<) 50 microgram per milliliter (microg/mL) and who are Week 6 non-responders based on partial Mayo score.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Has a diagnosis of UC established at least 1 month prior to Screening by clinical andendoscopic evidence and corroborated by a histopathology report.
  2. Has moderately to severely active UC as determined by a complete Mayo score of 6 to 12with an endoscopic subscore ≥2 within 28 days prior to enrollment.
  3. Has evidence of UC proximal to the rectum (≥15 cm of involved colon) prior to start ofvedolizumab IV dosing.
  4. Has been determined to be suitable for vedolizumab IV for routine management of UC bytheir physician.
  5. Has a family history of colorectal cancer, personal history of increased colorectalcancer risk, age >50 years, or other known risk factor must be up-to-date oncolorectal cancer surveillance (may be performed during screening).
  6. Has demonstrated an inadequate response with, lost response to, or intolerance of atleast 1 of the following agents: immunomodulators, corticosteroids, or tumor necrosisfactor-alpha (TNF-α) antagonists. Subject who are naive to TNF-α antagonist therapy orwho have previously failed TNF-α antagonist therapy (including primary and secondarynon-responders or intolerant) may be included. Week 6 Randomized Treatment Period Inclusion Criteria
  7. Following Lead-in Period, the subject is assessed as having high vedolizumab drugclearance based on a predefined Week 5 serum vedolizumab concentration threshold (<50microg/mL).
  8. Following Lead-in Period, the subject is a non-responder based on partial Mayo scoreat Week 6.

Exclusion

Exclusion Criteria:

  1. Has clinical evidence of abdominal abscess or toxic megacolon at the Screening Visit.
  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 microscopiccolitis.
  5. Has received any of the following for the treatment of underlying disease within 30days of screening:
  6. Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide)
  7. An approved non-biologic therapy in an investigational protocol.
  8. Has received any investigational or approved biologic or biosimilar agent within 60days or 5 half-lives prior to screening (whichever is longer).
  9. Has previously had prior exposure to approved or investigational anti-integrinantibodies (e.g. natalizumab, efalizumab, etrolizumab, AMG-181, anti-MAdCAM-1antibodies or rituximab).
  10. Has previously received approved or investigational vedolizumab.
  11. The subject currently requires or is anticipated to require surgical intervention forUC during the study.
  12. Has history or evidence of adenomatous colonic polyps that have not been removed, orcolonic mucosal dysplasia.
  13. Has any evidence of an active infection during Screening (eg, sepsis, cytomegalovirus,or listeriosis).
  14. Has a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 daysprior to screening, or ongoing chronic infection.
  15. Has evidence of active C. difficile as evidenced by positive C. difficile toxin or ishaving treatment for C. difficile infection or other intestinal pathogens duringScreening.
  16. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or chronic HBV (HBV immune subjects (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included), orhepatitis C virus (HCV) infection. Subjects with documented successful treatment ofHCV with sustained virological response (SVR) at 26 weeks can be enrolled.
  17. Has active or latent tuberculosis (TB), as evidenced by the following: a. A diagnostic TB test performed within 30 days of screening or during the ScreeningPeriod that is positive, defined as: i. Positive QuantiFERON test or 2 successiveindeterminate QuantiFERON tests, OR ii. A TB skin test reaction ≥ 5 mm OR, b. ChestX-ray within 3 months of screening that is suspicious for pulmonary TB, and a positiveor 2 successive indeterminate QuantiFERON tests within 30 days prior to Screening orduring the Screening Period.
  18. Has any identified congenital or acquired immunodeficiency (eg, common variableimmunodeficiency, HIV infection, organ transplantation).
  19. Has any live vaccination within 30 days prior to Screening or is planning to receiveany live vaccination during participation in the study.
  20. Has used a topical (rectal) treatment with (5-ASA) or corticosteroidenemas/suppositories within 2 weeks prior to Screening.
  21. Has a history of hypersensitivity or allergies to vedolizumab IV or its components.
  22. Has received total parenteral nutrition (TPN) or albumin in the last 30 days prior toscreening.
  23. Has any unstable or uncontrolled cardiovascular disorder, heart failure moderate tosevere (New York Class Association III or IV), any pulmonary, hepatic, renal, GI,genitourinary, hematological, coagulation, immunological, endocrine/metabolic, orother medical disorder that, in the opinion of the investigator, would confound thestudy results or compromise subject safety.
  24. Has had a surgical procedure requiring general anesthesia within 30 days prior toscreening or is planning to undergo major surgery during the study period.
  25. Has a history of malignancy, except for the following: adequately-treatednon-metastatic basal cell skin cancer; squamous cell skin cancer that has beenadequately 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 thathas not recurred for at least 3 years prior to screening. Subjects with remote historyof 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 andmust be discussed with the sponsor on a case by-case basis prior to Screening.
  26. Has a history of any major neurological disorders, including stroke, multiplesclerosis, brain tumor, demyelinating, or neurodegenerative disease.
  27. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptomchecklist during Screening or prior to the administration of the first dose of studydrug on Day 1.
  28. Has a history of drug abuse (defined as any illicit drug use) or a history of alcoholabuse within 1 year prior to the Screening Visit.

Study Design

Total Participants: 278
Treatment Group(s): 1
Primary Treatment: Vedolizumab IV
Phase: 4
Study Start date:
March 29, 2017
Estimated Completion Date:
October 16, 2020

Study Description

The drug being tested in this study is called Vedolizumab. Vedolizumab will be administered as an IV infusion. It is being tested in this study with new doses. This study will investigate the efficacy and safety of dose optimization of vedolizumab IV, compared with standard dosing of vedolizumab IV, over a 30-week treatment period.

The study will enroll approximately 250 moderately to severely active subjects with UC in order to randomize approximately 100 non-responder subjects with high vedolizumab drug clearance. Subjects will receive induction therapy of vedolizumab IV 300 mg on Day 1 and Week 2 (Lead-in Period). At Week 5, serum vedolizumab concentration will be measured. At Week 6, subjects will be assessed for clinical response based on partial Mayo score.

Results of both Week 5 vedolizumab concentration and Week 6 clinical response will determine the treatment pathway. Those who are non-responders based on partial Mayo score at Week 6 and who are assessed as having high vedolizumab clearance, based on a predefined Week 5 serum vedolizumab concentration threshold (<50 microg/mL) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

  • Vedolizumab IV Standard Treatment

  • Vedolizumab IV Dose Optimized

All randomized subjects will receive vedolizumab IV either 300 mg or 600 mg every 4 or 8 weeks.

This multi-center trial will be conducted in United States of America and Canada. The overall time to participate in this study is 56 weeks. Subjects will make multiple visits to the clinic, and will be contacted by telephone, 6 months after last dose of study drug for a long term follow-up safety survey.

Connect with a study center

  • South Edmonton Gastorenterology

    Edmonton, Alberta T6L 6K3
    Canada

    Site Not Available

  • PerCuro Clinical Research Ltd.

    Victoria, British Colombia V8V 3M9
    Canada

    Site Not Available

  • Brandon Medical Arts Clinic

    Brandon, Manitoba R7A 0N7
    Canada

    Site Not Available

  • LHSC - University Hospital

    London, Ontario N6A 5A5
    Canada

    Site Not Available

  • LHSC - Victoria Hospital

    London, Ontario N6A 5W9
    Canada

    Site Not Available

  • Taunton Surgical Centre

    Oshawa, Ontario L1H 7K4
    Canada

    Site Not Available

  • Toronto Digestive Disease Associates, Inc.

    Vaughan, Ontario L4L4Y7
    Canada

    Site Not Available

  • Digestive Health Specialist of the Southeast

    Dothan, Alabama 36305
    United States

    Site Not Available

  • IMC-Diagnostic& Medical Clinic

    Mobile, Alabama 36604
    United States

    Site Not Available

  • Digestive Health Research Unit

    Scottsdale, Arizona 85251
    United States

    Site Not Available

  • Advanced Clinical Therapeutics, LLC

    Tucson, Arizona 85712
    United States

    Site Not Available

  • Arkansas Primary Care Clinic, PA

    Little Rock, Arkansas 72204
    United States

    Site Not Available

  • SC Clinical Research Inc

    Garden Grove, California 92844
    United States

    Site Not Available

  • Care Access Research LLC

    San Pablo, California 94806
    United States

    Site Not Available

  • Care Access Research, San Pablo

    San Pablo, California 94806
    United States

    Site Not Available

  • Gastroenterology Associates of Fairfield County

    Bridgeport, Connecticut 06066
    United States

    Site Not Available

  • Gastro Florida

    Clearwater, Florida 33756
    United States

    Site Not Available

  • Florida Research Network, LLC

    Gainesville, Florida 32605
    United States

    Site Not Available

  • Wellness Clinical Research, LLC

    Hialeah, Florida 33016
    United States

    Site Not Available

  • Sarkis Medical

    Lake City, Florida 32055
    United States

    Site Not Available

  • Center for Advanced Gastro

    Maitland, Florida 32751
    United States

    Site Not Available

  • Center for Interventional Endo

    Orlando, Florida 32803
    United States

    Site Not Available

  • BRCR Medical Center, Inc.

    Pembroke Pines, Florida 33028
    United States

    Site Not Available

  • Advanced Medical Research Center

    Port Orange, Florida 32127
    United States

    Site Not Available

  • Gastro Florida

    Tampa, Florida 33626
    United States

    Site Not Available

  • Atlanta Gastroenterology Specialists, PC

    Atlanta, Georgia 30308
    United States

    Site Not Available

  • Atlanta Center for Gastroenterology

    Decatur, Georgia 30033
    United States

    Site Not Available

  • Meridian Clinical Research, LLC

    Savannah, Georgia 31406
    United States

    Site Not Available

  • Grand Teton Research Group, PLLC

    Idaho Falls, Idaho 83404
    United States

    Site Not Available

  • Nortwstrn Feinberg Schl of Med

    Chicago, Illinois 60611
    United States

    Site Not Available

  • NorthShore University HealthSystem

    Evanston, Illinois 60201
    United States

    Site Not Available

  • Aquiant Research

    New Albany, Indiana 47150
    United States

    Site Not Available

  • Iowa Digestive disease center

    Clive, Iowa 50325
    United States

    Site Not Available

  • Cotton O'Neil Clinical Research Center

    Topeka, Kansas 66604
    United States

    Site Not Available

  • Gastroeneterology Associates of of Hazards

    Hazard, Kentucky 41701
    United States

    Site Not Available

  • Gastroenterology Associates LLC

    Baton Rouge, Louisiana 70809
    United States

    Site Not Available

  • 3801 Houma Blvd. Ste 200

    Metairie, Louisiana 70006
    United States

    Site Not Available

  • Louisiana Research Center, LLC

    Shreveport, Louisiana 71105
    United States

    Site Not Available

  • 4940 Eastern Ave A building

    Baltimore, Maryland 21224
    United States

    Site Not Available

  • Chevy Chase clinical research

    Chevy Chase, Maryland 20815
    United States

    Site Not Available

  • Gastro Center of Maryland

    Columbia, Maryland 20721
    United States

    Site Not Available

  • Woodholme Gastroenterology Associates

    Glen Burnie, Maryland 21061
    United States

    Site Not Available

  • Oakland Medical Research Center

    Troy, Michigan 48085
    United States

    Site Not Available

  • University of Minnesota

    Minneapolis, Minnesota 55455
    United States

    Site Not Available

  • Las Vegas Medical Research

    Las Vegas, Nevada 89113
    United States

    Site Not Available

  • Center for Digestive Health

    Pennington, New Jersey 88534
    United States

    Site Not Available

  • AccumetRx Research

    Albuquerque, New Mexico 87109
    United States

    Site Not Available

  • NYU Langone Long Island Clinic

    Great Neck, New York 11021
    United States

    Site Not Available

  • Weill Cornell Medical College

    New York, New York 10065
    United States

    Site Not Available

  • Premier Medical Group of the Hudson Valley

    Poughkeepsie, New York 12601
    United States

    Site Not Available

  • Charlotte Gastroenterology and Hepatology

    Charlotte, North Carolina 28207
    United States

    Site Not Available

  • Dayton Gastroenterology, Inc

    Dayton, Ohio 45415
    United States

    Site Not Available

  • University of Pennsylvania Health System

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • Gastroenterology Associates PA

    Greenville, South Carolina 29615
    United States

    Site Not Available

  • Midwest Medical Care

    Sioux Falls, South Dakota 57105
    United States

    Site Not Available

  • Vanderbilt Medical Center

    Nashville, Tennessee 37212
    United States

    Site Not Available

  • Aztec Medical Research LLC

    Channelview, Texas 77530
    United States

    Site Not Available

  • Texas Digestive Disease Consultants - Dallas

    Dallas, Texas 75231
    United States

    Site Not Available

  • Ygenics

    Decatur, Texas 76234
    United States

    Site Not Available

  • Baylor College of Medicine

    Houston, Texas 77030
    United States

    Site Not Available

  • Texas Digestive Disease Consultants

    Keller, Texas 76248
    United States

    Site Not Available

  • DHAT Research Institute

    Richardson, Texas 75082
    United States

    Site Not Available

  • Texas Digestive Disease Consultants - Southlake

    Southlake, Texas 76092
    United States

    Site Not Available

  • BaylorScott&White Research Institute

    Temple, Texas 76508
    United States

    Site Not Available

  • GI Liver Research LLC

    Webster, Texas 77598
    United States

    Site Not Available

  • Care Access Research

    Salt Lake City, Utah 84124
    United States

    Site Not Available

  • Gastroenterology Associates of Tidewater

    Chesapeake, Virginia 23320
    United States

    Site Not Available

  • Gastroenterology Associates of Northern Virginia, Ltd.

    Fairfax, Virginia 22031
    United States

    Site Not Available

  • 121 Nationwide Dr., Ste. A

    Lynchburg, Virginia 24502
    United States

    Site Not Available

  • Digestive and Liver Disease Specialists, Ltd.

    Norfolk, Virginia 23502
    United States

    Site Not Available

  • McGuire Research Institute

    Richmond, Virginia 23249
    United States

    Site Not Available

  • Swedish Medical Center

    Seattle, Washington 98104
    United States

    Site Not Available

  • Medical College of Wisconsin, Inc.

    Milwaukee, Wisconsin 53266
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.