Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis
ENTERPRET
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)
2 other identifiers
interventional
278
2 countries
49
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Mar 2017
Longer than P75 for phase_4
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2017
CompletedFirst Posted
Study publicly available on registry
January 24, 2017
CompletedStudy Start
First participant enrolled
March 29, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 16, 2020
CompletedResults Posted
Study results publicly available
November 11, 2021
CompletedJuly 28, 2023
July 1, 2023
3.6 years
January 20, 2017
October 15, 2021
July 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Achieving Mucosal Healing at Week 30
Mucosal healing is defined as Mayo endoscopic subscore \<=1 point. Mayo score was used in clinical trials to assess UC disease activity. It consisted of 4 disease activity variables (stool frequency, rectal bleeding, findings on sigmoidoscopy and physician's global assessment), each scored on a scale of 0 to 3, where 0 normal condition and 3 = severe disease condition. The total Mayo score ranges from 0 to 12, with higher scores indicating more severe disease.
Week 30
Secondary Outcomes (5)
Percentage of Participants Achieving Clinical Remission at Week 30
Week 30
Percentage of Participants Achieving Clinical Response at Week 30
Week 30
Percentage of Participants Achieving Clinical Response at Week 14
Week 14
Percentage of Participants Achieving Corticosteroid-Free Remission
Week 30
Percentage of Participants Achieving Durable Clinical Response
Weeks 14 and 30
Study Arms (3)
Lead-in Period: Vedolizumab 300 mg
EXPERIMENTALVedolizumab 300 mg intravenous (IV) infusion once at Day 1 and at Week 2. Participants who were non-responders based on partial Mayo score at Week 6 and who had high vedolizumab clearance (\>0.14 L/day) at Week 5 were eligible for Randomized Treatment Period (RTP). Participants who were responders (Lead-In Failures) entered the 18-week follow-up period and discontinued the study.
Randomized Treatment Period (RTP): Standard Treatment Arm
EXPERIMENTALFollowing Lead-in Period, participants received vedolizumab 300 mg, IV infusion, once every 8 weeks (Q8W) at Weeks 6, 14 and 22 as standard treatment plus 18 weeks follow-up.
RTP: Dose Optimized Arm
EXPERIMENTALFollowing Lead-in Period, participants received vedolizumab 600 mg, IV infusion at Week 6, followed by Regimen A: vedolizumab 300 mg once in every 4 weeks (Q4W) thereafter (Weeks 10, 14, 18, 22 and 26) plus 18 weeks follow-up, or Regimen B: vedolizumab 600 mg, IV infusion Q4W (Weeks 10, 14, 18, 22 and 26) plus 18 weeks follow-up based on drug clearance.
Interventions
Vedolizumab intravenous infusion.
Eligibility Criteria
You may qualify if:
- Has a diagnosis of UC established at least 1 month prior to Screening by clinical and endoscopic evidence and corroborated by a histopathology report.
- 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.
- Has evidence of UC proximal to the rectum (≥15 cm of involved colon) prior to start of vedolizumab IV dosing.
- Has been determined to be suitable for vedolizumab IV for routine management of UC by their physician.
- 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).
- 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.
- 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).
- Following Lead-in Period, the subject is a non-responder based on partial Mayo score at Week 6.
You may not qualify if:
- Has clinical evidence of abdominal abscess or toxic megacolon at the Screening Visit.
- Has had an extensive colonic resection, subtotal or total colectomy.
- Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
- Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
- Has received any of the following for the treatment of underlying disease within 30 days of screening:
- Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide)
- An approved non-biologic therapy in an investigational protocol.
- Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives prior to screening (whichever is longer).
- 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).
- Has previously received approved or investigational vedolizumab.
- The subject currently requires or is anticipated to require surgical intervention for UC during the study.
- Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia.
- Has any evidence of an active infection during Screening (eg, sepsis, cytomegalovirus, or listeriosis).
- Has a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection.
- 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 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (49)
Advanced Clinical Therapeutics, LLC
Tucson, Arizona, 85712, United States
Arkansas Primary Care Clinic, PA
Little Rock, Arkansas, 72204, United States
Care Access Research LLC
San Pablo, California, 94806, United States
Care Access Research, San Pablo
San Pablo, California, 94806, United States
Gastroenterology Associates of Fairfield County
Bridgeport, Connecticut, 06066, United States
Gastro Florida
Clearwater, Florida, 33756, United States
Florida Research Network, LLC
Gainesville, Florida, 32605, United States
Wellness Clinical Research, LLC
Hialeah, Florida, 33016, United States
Center for Advanced Gastro
Maitland, Florida, 32751, United States
Center for Interventional Endo
Orlando, Florida, 32803, United States
BRCR Medical Center, Inc.
Pembroke Pines, Florida, 33028, United States
Gastro Florida
Tampa, Florida, 33626, United States
Atlanta Gastroenterology Specialists, PC
Atlanta, Georgia, 30308, United States
Atlanta Center for Gastroenterology
Decatur, Georgia, 30033, United States
Grand Teton Research Group, PLLC
Idaho Falls, Idaho, 83404, United States
NorthShore University HealthSystem
Evanston, Illinois, 60201, United States
Aquiant Research
New Albany, Indiana, 47150, United States
Iowa Digestive disease center
Clive, Iowa, 50325, United States
Cotton O'Neil Clinical Research Center
Topeka, Kansas, 66604, United States
Gastroenterology Associates LLC
Baton Rouge, Louisiana, 70809, United States
Louisiana Research Center, LLC
Shreveport, Louisiana, 71105, United States
4940 Eastern Ave A building
Baltimore, Maryland, 21224, United States
Gastro Center of Maryland
Columbia, Maryland, 20721, United States
Woodholme Gastroenterology Associates
Glen Burnie, Maryland, 21061, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Las Vegas Medical Research
Las Vegas, Nevada, 89113, United States
Weill Cornell Medical College
New York, New York, 10065, United States
Charlotte Gastroenterology and Hepatology
Charlotte, North Carolina, 28207, United States
Dayton Gastroenterology, Inc
Dayton, Ohio, 45415, United States
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104, United States
Gastroenterology Associates PA
Greenville, South Carolina, 29615, United States
Midwest Medical Care
Sioux Falls, South Dakota, 57105, United States
Vanderbilt Medical Center
Nashville, Tennessee, 37212, United States
Texas Digestive Disease Consultants - Dallas
Dallas, Texas, 75231, United States
Ygenics
Decatur, Texas, 76234, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Texas Digestive Disease Consultants
Keller, Texas, 76248, United States
DHAT Research Institute
Richardson, Texas, 75082, United States
Texas Digestive Disease Consultants - Southlake
Southlake, Texas, 76092, United States
BaylorScott&White Research Institute
Temple, Texas, 76508, United States
GI Liver Research LLC
Webster, Texas, 77598, United States
Gastroenterology Associates of Northern Virginia, Ltd.
Fairfax, Virginia, 22031, United States
Swedish Medical Center
Seattle, Washington, 98104, United States
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53266, United States
PerCuro Clinical Research Ltd.
Victoria, British Colombia, V8V 3M9, Canada
LHSC - University Hospital
London, Ontario, N6A 5A5, Canada
LHSC - Victoria Hospital
London, Ontario, N6A 5W9, Canada
Taunton Surgical Centre
Oshawa, Ontario, L1H 7K4, Canada
Toronto Digestive Disease Associates, Inc.
Vaughan, Ontario, L4L4Y7, Canada
Related Publications (1)
Jairath V, Yarur A, Osterman MT, James A, Balma D, Mehrotra S, Yang L, Yajnik V, Qasim Khan RM. ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse. Clin Gastroenterol Hepatol. 2024 May;22(5):1077-1086.e13. doi: 10.1016/j.cgh.2023.10.029. Epub 2023 Nov 10.
PMID: 37951560DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 20, 2017
First Posted
January 24, 2017
Study Start
March 29, 2017
Primary Completion
October 16, 2020
Study Completion
October 16, 2020
Last Updated
July 28, 2023
Results First Posted
November 11, 2021
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.