Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis



Status:Recruiting
Conditions:Colitis, Colitis, Gastrointestinal
Therapuetic Areas:Gastroenterology
Healthy:No
Age Range:18 - 85
Updated:3/6/2019
Start Date:March 29, 2017
End Date:June 30, 2020
Contact:Takeda Study Registration Call Center
Email:medicalinformation@tpna.com
Phone:+1-877-825-3327

Use our guide to learn which trials are right for you!

A Phase 4 Open-Label Study to Evaluate Vedolizumab IV Dose Optimization on Treatment Outcomes In Nonresponders With Moderately to Severely Active Ulcerative Colitis (ENTERPRET)

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 subjects 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.

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.

Inclusion Criteria:

1. Has a diagnosis of UC established at least 1 month prior to Screening by clinical and
endoscopic evidence and corroborated by a histopathology report.

2. Has moderately to severely active UC as determined by a complete Mayo score of 6 to 12
with 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 of
vedolizumab IV dosing.

4. Has been determined to be suitable for vedolizumab IV for routine management of UC by
their physician.

5. Has a family history of colorectal cancer, personal history of increased colorectal
cancer risk, age >50 years, or other known risk factor must be up-to-date on
colorectal cancer surveillance (may be performed during screening).

6. Has demonstrated an inadequate response with, lost response to, or intolerance of at
least 1 of the following agents: immunomodulators, corticosteroids, or tumor necrosis
factor-alpha (TNF-α) antagonists. Subject who are naive to TNF-α antagonist therapy or
who have previously failed TNF-α antagonist therapy (including primary and secondary
non-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 drug
clearance based on a predefined Week 5 serum vedolizumab concentration threshold (<50
microg/mL).

8. Following Lead-in Period, the subject is a non-responder based on partial Mayo score
at Week 6.

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 microscopic
colitis.

5. Has received any of the following for the treatment of underlying disease within 30
days of screening:

1. Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide)

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 screening (whichever is longer).

7. Has previously had prior exposure to approved or investigational anti-integrin
antibodies (e.g. natalizumab, efalizumab, etrolizumab, AMG-181, anti-MAdCAM-1
antibodies or rituximab).

8. Has previously received approved or investigational vedolizumab.

9. The subject currently requires or is anticipated to require surgical intervention for
UC during the study.

10. Has history or evidence of adenomatous colonic polyps that have not been removed, or
colonic mucosal dysplasia.

11. Has any evidence of an active infection during Screening (eg, sepsis, cytomegalovirus,
or listeriosis).

12. Has a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days
prior to screening, or ongoing chronic infection.

13. Has evidence of active C. difficile as evidenced by positive C. difficile toxin or is
having treatment for C. difficile infection or other intestinal pathogens during
Screening.

14. 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), or
hepatitis C virus (HCV) infection. Subjects with documented successful treatment of
HCV with sustained virological response (SVR) at 26 weeks can be enrolled.

15. 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 Screening
Period that is positive, defined as: i. Positive QuantiFERON test or 2 successive
indeterminate QuantiFERON tests, OR ii. A TB skin test reaction ≥ 5 mm OR, b. Chest
X-ray within 3 months of screening that is suspicious for pulmonary TB, and a positive
or 2 successive indeterminate QuantiFERON tests within 30 days prior to Screening or
during the Screening Period.

16. Has any identified congenital or acquired immunodeficiency (eg, common variable
immunodeficiency, HIV infection, organ transplantation).

17. Has any live vaccination within 30 days prior to Screening or is planning to receive
any live vaccination during participation in the study.

18. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid
enemas/suppositories within 2 weeks prior to Screening.

19. Has a history of hypersensitivity or allergies to vedolizumab IV or its components.

20. Has received total parenteral nutrition (TPN) or albumin in the last 30 days prior to
screening.

21. Has any unstable or uncontrolled cardiovascular disorder, heart failure moderate to
severe (New York Class Association III or IV), any pulmonary, hepatic, renal, GI,
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or
other medical disorder that, in the opinion of the investigator, would confound the
study results or compromise subject safety.

22. Has had a surgical procedure requiring general anesthesia within 30 days prior to
screening or is planning to undergo major surgery during the study period.

23. Has a history of malignancy, except for the following: adequately-treated
non-metastatic 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. Subjects with 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 and
must be discussed with the sponsor on a case by-case basis prior to Screening.

24. Has a history of any major neurological disorders, including stroke, multiple
sclerosis, brain tumor, demyelinating, or neurodegenerative disease.

25. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom
checklist during Screening or prior to the administration of the first dose of study
drug on Day 1.

26. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse within 1 year prior to the Screening Visit.
We found this trial at
59
sites
505 Nolen Drive
Southlake, Texas 76092
?
mi
from
Southlake, TX
Click here to add this to my saved trials
1200 Moursund Street
Houston, Texas 77030
(713) 798-4951
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
?
mi
from
Houston, TX
Click here to add this to my saved trials
Minneapolis, Minnesota 55455
(612) 625-5000
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
?
mi
from
Minneapolis, MN
Click here to add this to my saved trials
Seattle, Washington 98104
(206) 543-2100
Univ of Washington Founded in 1861 by a private gift of 10 acres in what...
?
mi
from
Seattle, WA
Click here to add this to my saved trials
823 SW Mulvane St
Topeka, Kansas 66606
785-368-0741
?
mi
from
Topeka, KS
Click here to add this to my saved trials
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Baltimore, Maryland 21224
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Baton Rouge, Louisiana 70809
?
mi
from
Baton Rouge, LA
Click here to add this to my saved trials
Bridgeport, Connecticut 06606
?
mi
from
Bridgeport, CT
Click here to add this to my saved trials
Charlotte, North Carolina 28207
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
Chevy Chase, Maryland 20815
?
mi
from
Chevy Chase, MD
Click here to add this to my saved trials
Chicago, Illinois 60611
?
mi
from
Chicago, IL
Click here to add this to my saved trials
5841 S Maryland Ave
Chicago, Illinois 60637
(773) 702-1000
University of Chicago Medical Center The University of Chicago Medicine has been at the forefront...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Clearwater, Florida 33762
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Clive, Iowa 50325
?
mi
from
Clive, IA
Click here to add this to my saved trials
Columbia, Maryland 21045
?
mi
from
Columbia, MD
Click here to add this to my saved trials
Dallas, Texas 75216
?
mi
from
Dallas, TX
Click here to add this to my saved trials
3409 Worth Street
Dallas, Texas 75231
?
mi
from
Dallas, TX
Click here to add this to my saved trials
1801 Inwood Rd
Dallas, Texas 75390
(214) 645-3300
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
?
mi
from
Dallas, TX
Click here to add this to my saved trials
Dayton, Ohio 45415
?
mi
from
Dayton, OH
Click here to add this to my saved trials
?
mi
from
Decatur, GA
Click here to add this to my saved trials
Decatur, Texas 76234
?
mi
from
Decatur, TX
Click here to add this to my saved trials
480 Honeysuckle Road
Dothan, Alabama 36305
?
mi
from
Dothan, AL
Click here to add this to my saved trials
?
mi
from
Edmonton,
Click here to add this to my saved trials
?
mi
from
Evanston, IL
Click here to add this to my saved trials
?
mi
from
Fairfax, VA
Click here to add this to my saved trials
Gainesville, Florida 32605
?
mi
from
Gainesville, FL
Click here to add this to my saved trials
Greenville, South Carolina 29615
?
mi
from
Greenville, SC
Click here to add this to my saved trials
?
mi
from
Hazard, KY
Click here to add this to my saved trials
8206 Northwest 103rd Street
Hialeah, Florida 33016
?
mi
from
Hialeah, FL
Click here to add this to my saved trials
Idaho Falls, Idaho 83404
?
mi
from
Idaho Falls, ID
Click here to add this to my saved trials
180 Bear Creek Parkway
Keller, Texas 76248
?
mi
from
Keller, TX
Click here to add this to my saved trials
Las Vegas, Nevada 89113
?
mi
from
Las Vegas, NV
Click here to add this to my saved trials
Little Rock, Arkansas 72204
?
mi
from
Little Rock, AR
Click here to add this to my saved trials
260 Lookout Place
Maitland, Florida 32751
?
mi
from
Maitland, FL
Click here to add this to my saved trials
Metairie, Louisiana 70006
?
mi
from
Metairie, LA
Click here to add this to my saved trials
8701 W Watertown Plank Rd
Milwaukee, Wisconsin
(414) 955-8296
Medical College of Wisconsin The Medical College (MCW) of Wisconsin is a major national research...
?
mi
from
Milwaukee, WI
Click here to add this to my saved trials
Nashville, Tennessee 37212
?
mi
from
Nashville, TN
Click here to add this to my saved trials
2630 Grant Line Road
New Albany, Indiana 47150
?
mi
from
New Albany, IN
Click here to add this to my saved trials
New York, New York 10021
?
mi
from
New York, NY
Click here to add this to my saved trials
601 East Rollins Street
Orlando, Florida 32803
?
mi
from
Orlando, FL
Click here to add this to my saved trials
12151 Taft Street
Pembroke Pines, Florida 33026
?
mi
from
Pembroke Pines, FL
Click here to add this to my saved trials
Pennington, New Jersey 88534
?
mi
from
Pennington, NJ
Click here to add this to my saved trials
111 S 11th St
Philadelphia, Pennsylvania 19107
(215) 955-6000
Thomas Jefferson University Hospital Our hospitals in Center City Philadelphia share a 13-acre campus with...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Philadelphia, Pennsylvania 19104
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
243 N Rd
Poughkeepsie, New York 12601
(845) 471-9410
Premier Medical Group of the Hudson Valley Premier Medical Group offers comprehensive, integrated care providing...
?
mi
from
Poughkeepsie, NY
Click here to add this to my saved trials
Richardson, Texas 75082
?
mi
from
Richardson, TX
Click here to add this to my saved trials
Richmond, Virginia 23249
?
mi
from
Richmond, VA
Click here to add this to my saved trials
1045 East 3900 South
Salt Lake City, Utah 84124
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
San Pablo, California 94806
?
mi
from
San Pablo, CA
Click here to add this to my saved trials
San Pablo, California 94806
?
mi
from
San Pablo, CA
Click here to add this to my saved trials
5300 Tallman Ave NW
Seattle, Washington 98122
(206) 782-2700
Swedish Medical Center Since 1910, Swedish has been the region's hallmark for excellence in health...
?
mi
from
Seattle, WA
Click here to add this to my saved trials
Shreveport, Louisiana 71103
?
mi
from
Shreveport, LA
Click here to add this to my saved trials
Sioux Falls, South Dakota 57108
?
mi
from
Sioux Falls, SD
Click here to add this to my saved trials
Tampa, Florida 33626
?
mi
from
Tampa, FL
Click here to add this to my saved trials
?
mi
from
Temple, TX
Click here to add this to my saved trials
Troy, Michigan 48085
?
mi
from
Troy, MI
Click here to add this to my saved trials
Tucson, Arizona 85712
?
mi
from
Tucson, AZ
Click here to add this to my saved trials
Webster, Texas 77598
?
mi
from
Webster, TX
Click here to add this to my saved trials