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Colitis, UlcerativePhase 4ENTERPRETNCT03029143

Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis

A Phase 4 study testing Vedolizumab IV in people with Colitis, Ulcerative, run by Takeda at 49 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Colitis, Ulcerative
What is being tested?
Vedolizumab IV
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
278 participants
Where
49 sitesin 2 countries
Study dates
29 Mar 2017to 16 Oct 2020
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • Week 6 Randomized Treatment Period Inclusion Criteria
  • 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.

Who cannot join

  • 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)
Show all 29Show fewer
  • 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.
  • 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.
  • Has active or latent tuberculosis (TB), as evidenced by the following:
  • 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.
  • Has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, HIV infection, organ transplantation).
  • Has any live vaccination within 30 days prior to Screening or is planning to receive any live vaccination during participation in the study.
  • Has used a topical (rectal) treatment with (5-ASA) or corticosteroid enemas/suppositories within 2 weeks prior to Screening.
  • Has a history of hypersensitivity or allergies to vedolizumab IV or its components.
  • Has received total parenteral nutrition (TPN) or albumin in the last 30 days prior to screening.
  • 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.
  • 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.
  • 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.
  • Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease.
  • 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.
  • 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.

Trial locations and contacts

49 sites in 2 countries.

49 sites in 2 countries

United States44 sites

  • Atlanta Gastroenterology Specialists, PC

    Atlanta, Georgia, 30308

  • 4940 Eastern Ave A building

    Baltimore, Maryland, 21224

  • Gastroenterology Associates LLC

    Baton Rouge, Louisiana, 70809

  • Gastroenterology Associates of Fairfield County

    Bridgeport, Connecticut, 06066

  • Charlotte Gastroenterology and Hepatology

    Charlotte, North Carolina, 28207

  • Gastro Florida

    Clearwater, Florida, 33756

  • Iowa Digestive disease center

    Clive, Iowa, 50325

  • Gastro Center of Maryland

    Columbia, Maryland, 20721

  • Texas Digestive Disease Consultants - Dallas

    Dallas, Texas, 75231

  • Dayton Gastroenterology, Inc

    Dayton, Ohio, 45415

  • Atlanta Center for Gastroenterology

    Decatur, Georgia, 30033

  • Ygenics

    Decatur, Texas, 76234

  • NorthShore University HealthSystem

    Evanston, Illinois, 60201

  • Gastroenterology Associates of Northern Virginia, Ltd.

    Fairfax, Virginia, 22031

  • Florida Research Network, LLC

    Gainesville, Florida, 32605

  • Woodholme Gastroenterology Associates

    Glen Burnie, Maryland, 21061

  • Gastroenterology Associates PA

    Greenville, South Carolina, 29615

  • Wellness Clinical Research, LLC

    Hialeah, Florida, 33016

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Grand Teton Research Group, PLLC

    Idaho Falls, Idaho, 83404

  • Texas Digestive Disease Consultants

    Keller, Texas, 76248

  • Las Vegas Medical Research

    Las Vegas, Nevada, 89113

  • Arkansas Primary Care Clinic, PA

    Little Rock, Arkansas, 72204

  • Center for Advanced Gastro

    Maitland, Florida, 32751

  • Medical College of Wisconsin, Inc.

    Milwaukee, Wisconsin, 53266

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt Medical Center

    Nashville, Tennessee, 37212

  • Aquiant Research

    New Albany, Indiana, 47150

  • Weill Cornell Medical College

    New York, New York, 10065

  • Center for Interventional Endo

    Orlando, Florida, 32803

  • BRCR Medical Center, Inc.

    Pembroke Pines, Florida, 33028

  • University of Pennsylvania Health System

    Philadelphia, Pennsylvania, 19104

  • DHAT Research Institute

    Richardson, Texas, 75082

  • Care Access Research LLC

    San Pablo, California, 94806

  • Care Access Research, San Pablo

    San Pablo, California, 94806

  • Swedish Medical Center

    Seattle, Washington, 98104

  • Louisiana Research Center, LLC

    Shreveport, Louisiana, 71105

  • Midwest Medical Care

    Sioux Falls, South Dakota, 57105

  • Texas Digestive Disease Consultants - Southlake

    Southlake, Texas, 76092

  • Gastro Florida

    Tampa, Florida, 33626

  • BaylorScott&White Research Institute

    Temple, Texas, 76508

  • Cotton O'Neil Clinical Research Center

    Topeka, Kansas, 66604

  • Advanced Clinical Therapeutics, LLC

    Tucson, Arizona, 85712

  • GI Liver Research LLC

    Webster, Texas, 77598

Other trials in United States

Canada5 sites

  • LHSC - University Hospital

    London, Ontario, N6A 5A5

  • LHSC - Victoria Hospital

    London, Ontario, N6A 5W9

  • Taunton Surgical Centre

    Oshawa, Ontario, L1H 7K4

  • Toronto Digestive Disease Associates, Inc.

    Vaughan, Ontario, L4L4Y7

  • PerCuro Clinical Research Ltd.

    Victoria, British Colombia, V8V 3M9

Other trials in Canada

About this study

Official title: 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 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.

Read the detailed 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.

Being tested
Vedolizumab IV
Keywords
Drug Therapy
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vedolizumab IVDrug

    Also called Entyvio, MLN0002

    Vedolizumab intravenous infusion.

Study groups in NCT03029143
Study groupRoleWhat they receive
Lead-in Period: Vedolizumab 300 mgExperimentalVedolizumab 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.
Receives: Drug: Vedolizumab IV
Randomized Treatment Period (RTP): Standard Treatment ArmExperimentalFollowing 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.
Receives: Drug: Vedolizumab IV
RTP: Dose Optimized ArmExperimentalFollowing 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.
Receives: Drug: Vedolizumab IV

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 30

Secondary outcomes (5)

  1. Percentage of Participants Achieving Clinical Remission at Week 30

    Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore >1 point at Week 30. 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.

    Measured: Week 30

  2. Percentage of Participants Achieving Clinical Response at Week 30

    Clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline (Day 1) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point, at Week 30. 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.

    Measured: Week 30

  3. Percentage of Participants Achieving Clinical Response at Week 14

    Clinical response is defined as A reduction in partial Mayo score of ≥2 points and ≥25% from Baseline (Day 1) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. Mayo score was used in clinical trials to assess UC disease activity. A composite index of 3 disease activity variables (stool frequency, rectal bleeding, and physician's global assessment), each scored on a scale from 0 to 3 with total partial Mayo score ranging from 0 to 9 (higher scores indicate greater disease activity). Partial Mayo score is calculated analogously to the complete Mayo score but excludes the sigmoidoscopy subscore.

    Measured: Week 14

  4. Percentage of Participants Achieving Corticosteroid-Free Remission

    Participants using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission. Mayo score was used in clinical trials to assess UC disease activity. Clinical Remission is defined as a complete Mayo score of <=2 points and no individual subscore >1 point at Week 30. 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.

    Measured: Week 30

  5. Percentage of Participants Achieving Durable Clinical Response

    A clinical response (based on partial Mayo score), which is defined as a reduction in partial Mayo score of ≥2 points and ≥25% from Baseline with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at Weeks 14 and 30. Mayo score was used in clinical trials to assess UC disease activity. A composite index of 3 disease activity variables (stool frequency, rectal bleeding, and physician's global assessment), each scored on a scale from 0 to 3 with total partial Mayo score ranging from 0 to 9 (higher scores indicate greater disease activity). Partial Mayo score is calculated analogously to the complete Mayo score but excludes the sigmoidoscopy subscore. Percentage of participants with durable clinical response, clinical response achieved at both Weeks 14 and 30 are reported.

    Measured: Weeks 14 and 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jan 2017 (estimated)
  2. Study start29 Mar 2017
  3. Primary completion16 Oct 2020
  4. Study completion16 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
278 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03029143
Sponsor's protocol ID
Vedolizumab-4014
Other IDs
U1111-1183-0451
Acronym
ENTERPRET
Status last verified
Jul 2023
First submitted
20 Jan 2017
Last updated
28 Jul 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 37951560

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vedolizumab IV in people with Colitis, Ulcerative, run by Takeda at 49 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Mucosal Healing at Week 30 (time frame: Week 30). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03029143, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2023.

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ENTERPRET Clinical Trial NCT03029143 | AzTrials