Determination of the Optimal Treatment Target in Ulcerative Colitis

NCT ID: NCT04259138

Last Updated: 2025-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

672 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-18

Study Completion Date

2026-03-31

Brief Summary

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Disease activity and response to therapy in ulcerative colitis (UC) can be assessed by a range of endpoints including symptoms, endoscopic mucosal activity, histological disease activity, and biomarkers. This study aims to determine the optimal treatment target, which is a research priority for the management of UC both to inform clinical practice and to help inform regulatory endpoints and targets for drug development.

Participants with active UC will be randomized in a 5:4:1 (initially 2:3:5) ratio to 1 of 3 groups, each with a different treatment target. Treatment targets will be defined as:

* Group 1: corticosteroid-free symptomatic remission
* Group 2: corticosteroid-free endoscopic + symptomatic remission
* Group 3: corticosteroid-free histological + endoscopic + symptomatic remission

An interim analysis was performed to assess the proportion of subjects that reached their assigned treatment target after 50 subjects in each group had reached the first 32-week assessment. The interim analysis and projections made based on target achievement rates for all subjects included in the interim analysis resulted in a recommendation to adjust the randomization ratio from 2:3:5 to 5:4:1 for Groups 1, 2 and 3 respectively as of May 5th, 2023. This change was necessary in order to complete the study with approximately 100 subjects achieving treatment target within each group.

Detailed Description

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Conditions

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Colitis, Ulcerative

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

In this study, participants with active UC will be randomized in a 5:4:1 ratio (initially 2:3:5) to 1 of 3 treatment target groups. Participants will be assigned a treatment algorithm based on their existing UC treatment at time of entry. Treatment algorithms may include the use of vedolizumab. A key premise is that vedolizumab has a favorable safety profile and can be used to treat participants who are in symptomatic remission but who have not attained endoscopic or histopathologic remission.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
Investigators will be trained on the treatment algorithms and target groups. Study participants will be blinded to target group assignment, whereas investigators will be unblinded.

Study Groups

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Symptomatic remission

Treatment target defined as achievement of corticosteroid-free symptomatic remission.

Group Type OTHER

Treatment Algorithm A

Intervention Type BIOLOGICAL

Participants who are not on UC treatment at screening (or who have only used topical therapy) will require standard first-line therapy. Either oral 5-ASA and/or immunosuppressive (azathioprine, 6-mercaptopurine, or methotrexate), with optional oral corticosteroid up to a maximum of 30 mg or prednisone or equivalent, will be initiated.

Treatment Algorithm B

Intervention Type BIOLOGICAL

Participants who are taking oral 5-ASA, immunosuppressive (azathioprine, 6-mercaptopurine, methotrexate), and/or oral corticosteroid at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Treatment Algorithm C

Intervention Type BIOLOGICAL

Participants who are taking a TNFα antagonist (infliximab, golimumab, or adalimumab), tofacitinib, or ustekinumab therapy at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Symptomatic and endoscopic remission

Treatment target defined as achievement of corticosteroid-free symptomatic remission plus endoscopic remission.

Group Type OTHER

Treatment Algorithm A

Intervention Type BIOLOGICAL

Participants who are not on UC treatment at screening (or who have only used topical therapy) will require standard first-line therapy. Either oral 5-ASA and/or immunosuppressive (azathioprine, 6-mercaptopurine, or methotrexate), with optional oral corticosteroid up to a maximum of 30 mg or prednisone or equivalent, will be initiated.

Treatment Algorithm B

Intervention Type BIOLOGICAL

Participants who are taking oral 5-ASA, immunosuppressive (azathioprine, 6-mercaptopurine, methotrexate), and/or oral corticosteroid at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Treatment Algorithm C

Intervention Type BIOLOGICAL

Participants who are taking a TNFα antagonist (infliximab, golimumab, or adalimumab), tofacitinib, or ustekinumab therapy at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Symptomatic, endoscopic and histological remission

Treatment target defined as achievement of corticosteroid-free symptomatic remission plus endoscopic remission plus histological remission.

Group Type OTHER

Treatment Algorithm A

Intervention Type BIOLOGICAL

Participants who are not on UC treatment at screening (or who have only used topical therapy) will require standard first-line therapy. Either oral 5-ASA and/or immunosuppressive (azathioprine, 6-mercaptopurine, or methotrexate), with optional oral corticosteroid up to a maximum of 30 mg or prednisone or equivalent, will be initiated.

Treatment Algorithm B

Intervention Type BIOLOGICAL

Participants who are taking oral 5-ASA, immunosuppressive (azathioprine, 6-mercaptopurine, methotrexate), and/or oral corticosteroid at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Treatment Algorithm C

Intervention Type BIOLOGICAL

Participants who are taking a TNFα antagonist (infliximab, golimumab, or adalimumab), tofacitinib, or ustekinumab therapy at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Interventions

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Treatment Algorithm A

Participants who are not on UC treatment at screening (or who have only used topical therapy) will require standard first-line therapy. Either oral 5-ASA and/or immunosuppressive (azathioprine, 6-mercaptopurine, or methotrexate), with optional oral corticosteroid up to a maximum of 30 mg or prednisone or equivalent, will be initiated.

Intervention Type BIOLOGICAL

Treatment Algorithm B

Participants who are taking oral 5-ASA, immunosuppressive (azathioprine, 6-mercaptopurine, methotrexate), and/or oral corticosteroid at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Intervention Type BIOLOGICAL

Treatment Algorithm C

Participants who are taking a TNFα antagonist (infliximab, golimumab, or adalimumab), tofacitinib, or ustekinumab therapy at screening will follow the treatment algorithm.

Participants will change to intravenous vedolizumab therapy.

Participants will be assessed to determine it remission target is achieved at weeks 16, 32 and 48. If the participant has achieved their treatment target, they will continue that line of therapy. If the participant has not achieved their treatment target, treatment and/or dose escalation will be administered according to the algorithm.

Intervention Type BIOLOGICAL

Other Intervention Names

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vedolizumab vedolizumab vedolizumab

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years.
2. Diagnosis of UC confirmed by clinical, endoscopic, and histological evidence prior to screening as per standard criteria.
3. Moderately to severely active UC with a Mayo rectal bleeding subscore ≥ 1 and a MES ≥ 2, with minimum disease extent of 15 cm and objective evidence of inflammation that can be visualized using central endoscopic imaging system.
4. Ability of participant to participate fully in all aspects of this clinical trial.
5. Written informed consent must be obtained and documented.
6. Agree not to participate in an investigational trial for the duration of the trial (observation or other noninterventional trials may be permitted at the discretion of the investigator).
7. Negative standard of care tuberculosis (TB) test and hepatitis B and C test prior to randomization unless negative results available from within 12 months prior.
8. A male participant who is nonsterilized\* and sexually active with a female partner of childbearing potential\* agrees to use adequate contraception\* from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
9. A female participant of childbearing potential\* who is sexually active with a nonsterilized\* male partner agrees to use routinely adequate contraception\* from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
10. Up to date with colorectal carcinoma surveillance according to local standards and guidelines. If a subject is not up to date at screening, a standard of care surveillance assessment may be performed during the screening period.
11. Participants who are not responding to their existing treatment for UC (Netherlands-specific criterion).

Exclusion Criteria

1. Participants who have historically failed (i.e., had an inadequate response with, lost response to, or were intolerant to) 2 or more compounds or classes of advanced therapeutic options (biologics or small molecules; e.g., anti-TNFs, ustekinumab, or tofacitinib) for the treatment of their UC.
2. Current or previous treatment with vedolizumab, etrolizumab, or natalizumab.
3. Topical therapy (corticosteroid or 5-aminosalicylate \[5-ASA\]) use within 2 weeks prior to screening endoscopy.
4. Change to oral corticosteroid dosing within 2 weeks prior to randomization or a corticosteroid dose of \> 30 mg of prednisone or equivalent at randomization.
5. Known diagnosis of CD, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
6. Short gut syndrome.
7. Positive stool culture for or active Clostridioides difficile infection (as demonstrated by positive toxin and/or antigen).
8. Known hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required.
9. Known active or latent TB; if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization.
10. Received any investigational drug within 30 days prior to randomization/target assignment.
11. Serious underlying disease other than UC that in the opinion of the investigator may interfere with the participant's ability to participate fully in the study or would compromise participant safety (such as history of malignancies, major neurological disorders, or any unstable or uncontrolled medical disorder).
12. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures.
13. The participant has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization.
14. Hypersensitivity to any excipient of vedolizumab.
15. Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.
16. History of HIV or positive test at screening (Italy-specific criterion).
17. Any other contraindication(s)to vedolizumab (Italy-specific criterion).
18. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 18 weeks after the last dose; or intending to donate ova during such time period.
19. If male, the participant intends to donate sperm during the course of this study or for 18 weeks after the last dose.
20. Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination during conduct of the study, except vaccination for coronavirus disease of 2019 (COVID-19).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda Development Center Americas, Inc.

INDUSTRY

Sponsor Role collaborator

Alimentiv Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vipul Jairath, MD

Role: PRINCIPAL_INVESTIGATOR

Alimentiv Inc.

Locations

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St. Joseph Mercy Hospital/Huron Gastroenterology Associates

Ypsilanti, Michigan, United States

Site Status

Icahn School of Medicine at Mt Sinai Hospital

New York, New York, United States

Site Status

New York-Presbyterian/Weill Cornell Medical Center

New York, New York, United States

Site Status

Digestive Health Partners - Asheville Gastroenterology Associate

Asheville, North Carolina, United States

Site Status

Atrium Health (Carolinas HealthCare)

Charlotte, North Carolina, United States

Site Status

Gomel Regional Clinical Hospital

Homyel, Homiel, Belarus

Site Status

Vitebsk Regional Clinical Hospital

Vitebsk, Vitebsk Oblast, Belarus

Site Status

Imelda Ziekenhuis Bonheiden

Bonheiden, Antwerp, Belgium

Site Status

University Hospital Ghent

Ghent, East Flanders, Belgium

Site Status

UZ Leuven - University Hospital Gasthuisberg

Leuven, Flemish Brabant, Belgium

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

GIRI (GI Research Institute)

Vancouver, British Columbia, Canada

Site Status

Barrie GI Associates Inc.

Barrie, Ontario, Canada

Site Status

McMaster University Medical Centre

Hamilton, Ontario, Canada

Site Status

London Health Sciences Centre - University Campus

London, Ontario, Canada

Site Status

LHSC - Victoria Hospital

London, Ontario, Canada

Site Status

ABP Research Services Corp.

Oakville, Ontario, Canada

Site Status

Taunton Surgical Centre

Oshawa, Ontario, Canada

Site Status

Toronto Immune and Digestive Health Institute (TIDHI)

Toronto, Ontario, Canada

Site Status

McGill University Health Centre (MUHC) Montreal General Hospital

Montreal, Quebec, Canada

Site Status

CH Saint Etienne Hopital Nord

Saint-Priest-en-Jarez, Auvergne-Rhône-Alpes, France

Site Status

CHU Besançon - Hôpital Jean Minjoz

Besançon, Bourgogne-Franche-Comté, France

Site Status

CHRU De Nancy - Hopital de Brabois

Vandœuvre-lès-Nancy, Grand Est, France

Site Status

CHRU de Lille - Hopital Claude Huriez

Lille, Hauts-de-France, France

Site Status

CHU de Bordeaux - Hopital Haut Leveque - Groupe Hospitalier Sud

Pessac, Nouvelle-Aquitaine, France

Site Status

CHRU Montpellier - Hopital Saint Eloi

Montpellier, Occitanie, France

Site Status

Azienda Ospedaliera - Polyclinico Sant'Orsola-Malpighi

Bologna, Emilia-Romagna, Italy

Site Status

Ospedale San Raffaele S.r.I.

Milan, Milan, Italy

Site Status

Istituto Clinico Humanitas

Rozzano, Milan, Italy

Site Status

Azienda Ospedaliera di Padova

Padua, Padua, Italy

Site Status

Policlinico Universitario Agostino Gemelli

Roma, Rome, Italy

Site Status

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status

Catharina Hospital

Eindhoven, North Brabant, Netherlands

Site Status

ETZ Hospital Tilburg

Tilburg, North Brabant, Netherlands

Site Status

Amsterdam UMC - Academisch Medisch Centrum

Amsterdam, North Holland, Netherlands

Site Status

Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszcz

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.

Torun, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

Gabinet Endoskopii Przewodu Pokarmowego

Krakow, Lesser Poland Voivodeship, Poland

Site Status

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, Masovian Voivodeship, Poland

Site Status

Endoskopia Sp. z.o.o.

Sopot, Pomeranian Voivodeship, Poland

Site Status

Sonomed Sp. z o.o. - Centrum Medyczne

Szczecin, West Pomeranian Voivodeship, Poland

Site Status

Szpital Miejski Sw. Jana Pawla II w Elblagu

Elblag, , Poland

Site Status

Oddział Gastroenterologiczny SP ZOZ w Łęcznej

Łęczna, , Poland

Site Status

Dniepropetrovsk State Medical Academy

Dnipro, , Ukraine

Site Status

Odesa Regional Clinical Hospital

Odesa, , Ukraine

Site Status

Ternopil City Communal Emergency Medical Care Hosp

Ternopil, , Ukraine

Site Status

Uzhhorod National University

Uzhhorod, , Ukraine

Site Status

Vinnytsia City Clinical Hospital #1, Dept of Gastroenterology

Vinnytsia, , Ukraine

Site Status

Vinnytsia M.I. Pyrohov Regional Clinical Hospital

Vinnytsia, , Ukraine

Site Status

City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU

Zaporizhzhia, , Ukraine

Site Status

Hampshire Hospitals NHS Foundation Trust - The Royal Hampshire County Hospital

Winchester, Hampshire, United Kingdom

Site Status

Oxford University Hospitals NHS Foundation - John Radcliffe Hospital

Headington, Oxford, United Kingdom

Site Status

University Hospitals Birmingham NHS Foundation Trust (UHB) - Queen Elizabeth Hospital Birmingham

Birmingham, West Midlands, United Kingdom

Site Status

Russells Hall Hospital

Dudley, West Midlands, United Kingdom

Site Status

Hull & East Yorkshire NHS Trust

Hull, Yorkshire, United Kingdom

Site Status

Barts Health NHS Trust / Whipps Cross University Hospital

Leytonstone, , United Kingdom

Site Status

Barts Health NHS Trust - Royal London Hospital

London, , United Kingdom

Site Status

University of Nottingham NHS Trust

Nottingham, , United Kingdom

Site Status

Countries

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United States Belarus Belgium Canada France Italy Netherlands Poland Ukraine United Kingdom

References

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Jairath V, Zou G, Wang Z, Adsul S, Colombel JF, D'Haens GR, Freire M, Moran GW, Peyrin-Biroulet L, Sandborn WJ, Sebastian S, Travis S, Vermeire S, Radulescu G, Sigler J, Hanzel J, Ma C, Sedano R, McFarlane SC, Arya N, Beaton M, Bossuyt P, Danese S, Green D, Harlan W 3rd, Horynski M, Klopocka M, Petroniene R, Silverberg MS, Wolanski L, Feagan BG. Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial. BMJ Open Gastroenterol. 2024 Feb 8;11(1):e001218. doi: 10.1136/bmjgast-2023-001218.

Reference Type BACKGROUND
PMID: 38336367 (View on PubMed)

Related Links

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https://bmjopengastro.bmj.com/content/11/1/e001218

Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial

Other Identifiers

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2019-002485-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RP1706

Identifier Type: -

Identifier Source: org_study_id

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