Determination of the Optimal Treatment Target in Ulcerative Colitis

NCT04259138 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: RP17062019-002485-12
• Study Type: interventional
• Target: 672
• Locations: 9 countries
• Sites: 56

Brief Summary

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.

Conditions

Colitis, Ulcerative

Outcome Measures

Primary Outcomes (1)

• Difference in Time to UC-related Complication Between Treatment Target Groups 1 and 3

  Time to UC-related complication starting when a participant reaches their assigned treatment target, compared between treatment target groups 1 and 3.

  From date of treatment target achievement until date of first UC-related complication until end of study (Week 96), whichever came first

Secondary Outcomes (18)

• Difference in Time to UC-related Complication Compared Between Treatment Target Groups 1 and 2.

  From date of treatment target achievement until date of first UC-related complication until end of study (Week 96), whichever came first

• Difference in Time to UC-related Complication Compared Between Treatment Target Groups 2 and 3.

  From date of treatment target achievement until date of first UC-related complication until end of study (Week 96), whichever came first

• Difference in time to UC-related complication compared between subgroups

  From date of treatment target achievement until date of first UC-related complication until end of study (Week 96), whichever came first

• Difference in Time to Achieve Treatment Target

  up to 96 weeks

• Fecal Calprotectin Levels

  Baseline, weeks 8, 16, 32, 48, and 96.

Study Arms (3)

Symptomatic remission

OTHER

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

Biological: Treatment Algorithm A; Biological: Treatment Algorithm B; Biological: Treatment Algorithm C

Symptomatic and endoscopic remission

OTHER

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

Biological: Treatment Algorithm A; Biological: Treatment Algorithm B; Biological: Treatment Algorithm C

Symptomatic, endoscopic and histological remission

OTHER

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

Biological: Treatment Algorithm A; Biological: Treatment Algorithm B; Biological: Treatment Algorithm C

Interventions

Treatment Algorithm A 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.

Also known as: vedolizumab

Symptomatic and endoscopic remission; Symptomatic remission; Symptomatic, endoscopic and histological remission

Treatment Algorithm B 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.

Also known as: vedolizumab

Symptomatic and endoscopic remission; Symptomatic remission; Symptomatic, endoscopic and histological remission

Treatment Algorithm C 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.

Also known as: vedolizumab

Symptomatic and endoscopic remission; Symptomatic remission; Symptomatic, endoscopic and histological remission

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Diagnosis of UC confirmed by clinical, endoscopic, and histological evidence prior to screening as per standard criteria.
• 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.
• Ability of participant to participate fully in all aspects of this clinical trial.
• Written informed consent must be obtained and documented.
• 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).
• 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.
• 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.
• 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.
• 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.
• Participants who are not responding to their existing treatment for UC (Netherlands-specific criterion).

You may not qualify if:

• 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.
• Current or previous treatment with vedolizumab, etrolizumab, or natalizumab.
• Topical therapy (corticosteroid or 5-aminosalicylate \[5-ASA\]) use within 2 weeks prior to screening endoscopy.
• Change to oral corticosteroid dosing within 2 weeks prior to randomization or a corticosteroid dose of \> 30 mg of prednisone or equivalent at randomization.
• Known diagnosis of CD, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
• Short gut syndrome.
• Positive stool culture for or active Clostridioides difficile infection (as demonstrated by positive toxin and/or antigen).
• Known hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required.
• 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.
• Received any investigational drug within 30 days prior to randomization/target assignment.
• 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).
• 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.
• The participant has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization.
• Hypersensitivity to any excipient of vedolizumab.
• Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.

Sponsors & Collaborators

• Alimentiv Inc.: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (58)

St. Joseph Mercy Hospital/Huron Gastroenterology Associates

Ypsilanti, Michigan, 48197, United States

Location

Icahn School of Medicine at Mt Sinai Hospital

New York, New York, 10029, United States

Location

New York-Presbyterian/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Digestive Health Partners - Asheville Gastroenterology Associate

Asheville, North Carolina, 28801, United States

Location

Atrium Health (Carolinas HealthCare)

Charlotte, North Carolina, 28204, United States

Location

Gomel Regional Clinical Hospital

Homyel, Homiel, 246029, Belarus

Location

Vitebsk Regional Clinical Hospital

Vitebsk, Vitebsk Oblast, 210037, Belarus

Location

Imelda Ziekenhuis Bonheiden

Bonheiden, Antwerp, 2820, Belgium

Location

University Hospital Ghent

Ghent, East Flanders, 9000, Belgium

Location

UZ Leuven - University Hospital Gasthuisberg

Leuven, Flemish Brabant, 3000, Belgium

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

GIRI (GI Research Institute)

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Barrie GI Associates Inc.

Barrie, Ontario, L4M 7G1, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8S 4L8, Canada

Location

London Health Sciences Centre - University Campus

London, Ontario, N6A 5A5, Canada

Location

LHSC - Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

ABP Research Services Corp.

Oakville, Ontario, L6L 5L7, Canada

Location

Taunton Surgical Centre

Oshawa, Ontario, L1J 0C7, Canada

Location

Toronto Immune and Digestive Health Institute (TIDHI)

Toronto, Ontario, M6A 3B4, Canada

Location

McGill University Health Centre (MUHC) Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

CH Saint Etienne Hopital Nord

Saint-Priest-en-Jarez, Auvergne-Rhône-Alpes, 42055, France

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, Bourgogne-Franche-Comté, 25000, France

Location

CHRU De Nancy - Hopital de Brabois

Vandœuvre-lès-Nancy, Grand Est, 54500, France

Location

CHRU de Lille - Hopital Claude Huriez

Lille, Hauts-de-France, 59037, France

Location

CHU de Bordeaux - Hopital Haut Leveque - Groupe Hospitalier Sud

Pessac, Nouvelle-Aquitaine, 33604, France

Location

CHRU Montpellier - Hopital Saint Eloi

Montpellier, Occitanie, 34295, France

Location

Azienda Ospedaliera - Polyclinico Sant'Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale San Raffaele S.r.I.

Milan, Milan, 20132, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

Azienda Ospedaliera di Padova

Padua, Padua, 35128, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, Rome, 00-168, Italy

Location

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Catharina Hospital

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

ETZ Hospital Tilburg

Tilburg, North Brabant, 5022 GC, Netherlands

Location

Amsterdam UMC - Academisch Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszcz

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168, Poland

Location

GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Gabinet Endoskopii Przewodu Pokarmowego

Krakow, Lesser Poland Voivodeship, 31009, Poland

Location

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, Masovian Voivodeship, 00-72, Poland

Location

Endoskopia Sp. z.o.o.

Sopot, Pomeranian Voivodeship, 81-756, Poland

Location

Sonomed Sp. z o.o. - Centrum Medyczne

Szczecin, West Pomeranian Voivodeship, 71-685, Poland

Location

Szpital Miejski Sw. Jana Pawla II w Elblagu

Elblag, 82300, Poland

Location

Oddział Gastroenterologiczny SP ZOZ w Łęcznej

Łęczna, 21-010, Poland

Location

Dniepropetrovsk State Medical Academy

Dnipro, Ukraine

Location

Odesa Regional Clinical Hospital

Odesa, Ukraine

Location

Ternopil City Communal Emergency Medical Care Hosp

Ternopil, Ukraine

Location

Uzhhorod National University

Uzhhorod, Ukraine

Location

Vinnytsia City Clinical Hospital #1, Dept of Gastroenterology

Vinnytsia, Ukraine

Location

Vinnytsia M.I. Pyrohov Regional Clinical Hospital

Vinnytsia, Ukraine

Location

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

Zaporizhzhia, 69065, Ukraine

Location

Hampshire Hospitals NHS Foundation Trust - The Royal Hampshire County Hospital

Winchester, Hampshire, SO22 5DG, United Kingdom

Location

Oxford University Hospitals NHS Foundation - John Radcliffe Hospital

Headington, Oxford, OX39DU, United Kingdom

Location

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

Birmingham, West Midlands, B15 2GW, United Kingdom

Location

Russells Hall Hospital

Dudley, West Midlands, DY1 2HQ, United Kingdom

Location

Hull & East Yorkshire NHS Trust

Hull, Yorkshire, HU3 2JZ, United Kingdom

Location

Barts Health NHS Trust / Whipps Cross University Hospital

Leytonstone, E11 1NR, United Kingdom

Location

Barts Health NHS Trust - Royal London Hospital

London, E1 1BB, United Kingdom

Location

University of Nottingham NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38336367 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Vipul Jairath, MD

  Alimentiv Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 6, 2020
• Study Start: February 18, 2020
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: January 27, 2026

Record last verified: 2026-01

Locations

FR (6); NL (4); PL (8); IT (5); GB (8); BE (3); US (5); CA (10); UA (7)