Determination of the Optimal Treatment Target in Ulcerative Colitis (VERDICT)

VERDICT: In actiVE Ulcerative Colitis, a RanDomIzed Controlled Trial for Determination of the Optimal Treatment Target

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.

Study Overview

• Status: Recruiting
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Biological: Treatment Algorithm A; Biological: Treatment Algorithm B; Biological: Treatment Algorithm C

• Study Type: Interventional
• Enrollment (Estimated): 660
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Luiza Nita; Phone Number: +31 20 5630 310; Email: verdictcsm@alimentiv.com

Study Locations

• Belarus
  • Homiel
    • Gomel, Homiel, Belarus, 246029
      • Active, not recruiting
      • Gomel Regional Clinical Hospital
  • Viciebsk
    • Vitebsk, Viciebsk, Belarus, 210037
      • Active, not recruiting
      • Vitebsk Regional Clinical Hospital
• Belgium
  • Antwerp
    • Bonheiden, Antwerp, Belgium, 2820
      • Recruiting
      • Imelda Ziekenhuis Bonheiden
      • Contact: Ils Van De Schoot
      • Principal Investigator: Peter Bossuyt, PhD, MD
  • East Flanders
    • Ghent, East Flanders, Belgium, 9000
      • Recruiting
      • University Hospital Ghent
      • Principal Investigator: Triana Lobaton Ortega, MD, PhD
      • Contact: Natalia Swietek
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven - University Hospital Gasthuisberg
      • Contact: Julie Thijs
      • Principal Investigator: Marc Ferrante, PhD, MD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Recruiting
      • University of Calgary
      • Contact: Nima Hamidi
      • Principal Investigator: Remo Panaccione, MD
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Recruiting
      • GIRI (GI Research Institute)
      • Principal Investigator: Brian Bressler, MD
      • Contact: Maria Ancheta-Schmit
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Recruiting
      • Barrie GI Associates Inc.
      • Contact: Colayna Harris-Mailloux
      • Principal Investigator: Rima Petroniene, MD, PhD
    • Hamilton, Ontario, Canada, L8S 4L8
      • Recruiting
      • McMaster University Medical Centre
      • Contact: Mitzi Lawrence
      • Principal Investigator: Smita Halder, MD
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Centre - University Campus
      • Contact: Heather Prins
      • Principal Investigator: Melanie Beaton, MD
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • LHSC - Victoria Hospital
      • Contact: Cindi Wessman
      • Principal Investigator: Terry Ponich, MD, FRCPC
    • Oakville, Ontario, Canada, L6L 5L7
      • Recruiting
      • ABP Research Services Corp.
      • Contact: Keshini Abeyewardene
      • Principal Investigator: Naveen Arya, MD, FRCPC
    • Oshawa, Ontario, Canada, L1J 0C7
      • Recruiting
      • Taunton Surgical Centre
      • Contact: Alana Carter
      • Principal Investigator: Daniel Green, MD
    • Toronto, Ontario, Canada, M6A 3B4
      • Recruiting
      • Toronto Immune and Digestive Health Institute (TIDHI)
      • Contact: Ajani Jeyakumar
      • Principal Investigator: Mark Silverberg, MD, PhD
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Recruiting
      • Centre de Recherche du CHUM
      • Principal Investigator: Robert Battat, MD
      • Contact: Karine Paupert
    • Montreal, Quebec, Canada, H3G 1A4
      • Recruiting
      • McGill University Health Centre (MUHC) Montreal General Hospital
      • Contact: Carolyne Lemieux
      • Principal Investigator: Talat Bessissow, MD
• France
  • Auvergne-Rhone-Alpes
    • Saint-Priest-en-Jarez, Auvergne-Rhone-Alpes, France, 42055
      • Recruiting
      • CH Saint Etienne Hopital Nord
      • Principal Investigator: Xavier Roblin, MD
      • Contact: Melanie Dupin
  • Bourgogne-Franche-Comte
    • Besançon, Bourgogne-Franche-Comte, France, 25000
      • Recruiting
      • CHU Besançon - Hôpital Jean Minjoz
      • Contact: Fanny Vaurie
      • Principal Investigator: Lucine Vuitton, MD, PhD
  • Grand Est
    • Vandœuvre-lès-Nancy, Grand Est, France, 54500
      • Recruiting
      • CHRU de Nancy - Hôpital de Brabois
      • Contact: Kahina Touabi
      • Principal Investigator: Benedicte Caron, MD
  • Hauts-de-France
    • Lille Cedex, Hauts-de-France, France, 59037
      • Recruiting
      • CHRU de Lille - Hopital Claude Huriez
      • Contact: Audrey Baillon
      • Principal Investigator: Maria Nachury, (Prof) MD, PhD
  • Nouvelle-Aquitaine
    • PESSAC cedex, Nouvelle-Aquitaine, France, 33604
      • Recruiting
      • CHU de Bordeaux - Hopital Haut Leveque - Groupe Hospitalier Sud
      • Principal Investigator: David Laharie, (Prof) MS, MD
      • Contact: Cavillon-Justin Elodie
  • Occitanie
    • MONTPELLIER cedex 05, Occitanie, France, 34295
      • Recruiting
      • CHRU Montpellier - Hopital Saint Eloi
      • Principal Investigator: Romain Altwegg, MD
      • Contact: Sylvianne Roncero
  • Provence-Alpes-Cote d'Azur
    • NICE Cedex 03, Provence-Alpes-Cote d'Azur, France, 6202
      • Withdrawn
      • CHU Nice - Hopital l'Archet II
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • Azienda Ospedaliera - Polyclinico Sant'Orsola-Malpighi
      • Contact: Eleonora Filippone
      • Principal Investigator: Paolo Gionchetti, MD
  • Milan
    • Milano, Milan, Italy, 20132
      • Recruiting
      • Ospedale San Raffaele S.r.I.
      • Principal Investigator: Silvio Danese, MD
      • Contact: Carmen Di Matteo
    • Rozzano, Milan, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
      • Contact: Patrizia Danieli
      • Principal Investigator: Alessandro Armuzzi, MD
  • Padua
    • Padova, Padua, Italy, 35128
      • Recruiting
      • Azienda Ospedaliera di Padova
      • Contact: Greta Lorenzon
      • Principal Investigator: Edoardo V Savarino, MD
  • Rome
    • Roma, Rome, Italy, 00-168
      • Recruiting
      • Policlinico Universitario Agostino Gemelli
      • Contact: Roberta Savini
      • Principal Investigator: Antonio Gasbarrini, MD
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Radboud University Nijmegen Medical Centre
      • Contact: Cynthia Jansen
      • Principal Investigator: Marjolijn Duijvestein, MD, PhD
  • North Brabant
    • Eindhoven, North Brabant, Netherlands, 5623 EJ
      • Recruiting
      • Catharina hospital
      • Principal Investigator: Lennard Gilissen, MD
      • Contact: Ramon Schreuder
    • Tilburg, North Brabant, Netherlands, 5022 GC
      • Recruiting
      • ETZ Hospital Tilburg
      • Contact: Dominique Bierens-Peters
      • Principal Investigator: Maurice Lutgens, MD, PhD
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Recruiting
      • Amsterdam UMC - Academisch Medisch Centrum
      • Contact: Marlou Braad
      • Principal Investigator: Geert D'Haens, MD, PHD
• Poland
  • Elblag, Poland, 82300
    • Recruiting
    • Szpital Miejski Sw. Jana Pawla II w Elblagu
    • Contact: Kamila Osak
    • Principal Investigator: Krzysztof Niezgoda, MD
  • Łęczna, Poland, 21-010
    • Recruiting
    • Oddział Gastroenterologiczny SP ZOZ w Łęcznej
    • Contact: Damian Sowa, MD
    • Principal Investigator: Lukasz Wolanski, MD
  • Kuyavian-Pomeranian
    • Bydgoszcz, Kuyavian-Pomeranian, Poland, 85-168
      • Recruiting
      • Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszcz
      • Contact: Marcin Manerowski
      • Principal Investigator: Maria Klopocka, MD, PhD
    • Torun, Kuyavian-Pomeranian, Poland, 87-100
      • Recruiting
      • GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.
      • Contact: Daria Kriks
      • Principal Investigator: Adam Kopon, MD
  • Lesser Poland
    • Krakow, Lesser Poland, Poland, 31009
      • Recruiting
      • Gabinet Endoskopii Przewodu Pokarmowego
      • Contact: Magdalena Ras
      • Principal Investigator: Piotr Walczak, MD
  • Lower Silesian
    • Wroclaw, Lower Silesian, Poland, 52-416
      • Recruiting
      • Centrum Medyczne Oporow
      • Contact: Piotr Klepacki
      • Principal Investigator: Radoslaw Kempinski, MD
  • Masovia
    • Warszawa, Masovia, Poland, 02-781
      • Withdrawn
      • National Oncology Institute Maria Sklodowskiej-Curie
    • Warszawa, Masovia, Poland, 03-580
      • Recruiting
      • NZOZ Vivamed
      • Contact: Magdalena Miecz
      • Principal Investigator: Robert Petryka, MD
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 00-72
      • Recruiting
      • WIP Warsaw IBD Point Profesor Kierkus
      • Contact: Arkadiusz Cichowski
      • Principal Investigator: Jaroslaw Kierkus, MD
  • Pomeranian
    • Gdańsk, Pomeranian, Poland, 80-214
      • Withdrawn
      • Uniwersyteckie Centrum Kliniczne
  • Pomorskie
    • Sopot, Pomorskie, Poland, 81-756
      • Recruiting
      • Endoskopia Sp. z.o.o.
      • Principal Investigator: Marek Horynski, MD, PhD
      • Contact: Lidia Zaszczyryńska
  • West Pomeranian
    • Szczecin, West Pomeranian, Poland, 71-685
      • Recruiting
      • Sonomed Sp. z o.o. - Centrum Medyczne
      • Contact: Thomasz Kwiecien
      • Principal Investigator: Anna Wiechowska-Kozlowska, MD
• Ukraine
  • Dnipro, Ukraine
    • Terminated
    • Dniepropetrovsk State Medical Academy
  • Odesa, Ukraine
    • Completed
    • Odesa Regional Clinical Hospital
  • Ternopil, Ukraine
    • Terminated
    • Ternopil City Communal Emergency Medical Care Hosp
  • Vinnytsia, Ukraine
    • Terminated
    • Vinnytsia City Clinical Hospital #1, Dept of Gastroenterology
  • Vinnytsia, Ukraine
    • Terminated
    • Vinnytsia M.I. Pyrohov Regional Clinical Hospital
  • Zaporizhzhia, Ukraine, 69065
    • Completed
    • City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU
  • Úzhgorod, Ukraine
    • Terminated
    • Uzhhorod National University
• United Kingdom
  • Leytonstone, United Kingdom, E11 1NR
    • Recruiting
    • Barts Health NHS Trust / Whipps Cross University Hospital
    • Principal Investigator: Syed Hoque, MD
    • Contact: Jessica Disney
  • London, United Kingdom, E1 1BB
    • Recruiting
    • Barts Health NHS Trust - Royal London Hospital
    • Contact: Irish Lee
    • Sub-Investigator: Gareth Parkes, MD
  • Nottingham, United Kingdom, NG7 2UH
    • Recruiting
    • University of Nottingham NHS Trust
    • Contact: Sheila Hirst
    • Principal Investigator: Gordon Moran, MD
  • East Midlands
    • Derby, East Midlands, United Kingdom, DE22 3NE
      • Recruiting
      • Derby Teaching Hospitals NHS Foundation Trust - Royal Derby Hospital
      • Contact: Catherine Addleton
      • Principal Investigator: Said Din, MD
  • Hampshire
    • Winchester, Hampshire, United Kingdom, SO22 5DG
      • Recruiting
      • Hampshire Hospitals NHS Foundation Trust - The Royal Hampshire County Hospital
      • Contact: Emma Levell
      • Principal Investigator: John Gordon, MD
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Recruiting
      • London North West University Healthcare NHS Trust - Northwick Park Hospital
      • Contact: Suzan Byaruhanga
      • Principal Investigator: Ailsa Hart, MD
  • Oxford
    • Headington, Oxford, United Kingdom, OX39DU
      • Recruiting
      • Oxford University Hospitals NHS Foundation - John Radcliffe Hospital
      • Contact: Chitra Velmurugan
      • Principal Investigator: Jack Satsangi, MD
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2GW
      • Recruiting
      • University Hospitals Birmingham NHS Foundation Trust (UHB) - Queen Elizabeth Hospital Birmingham
      • Contact: Louise Bowlas
      • Principal Investigator: Rachel Cooney, MD
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Recruiting
      • Russells Hall Hospital
      • Contact: Clare Allcock
      • Principal Investigator: Shanika De Silva, MD
  • Yorkshire
    • Hull, Yorkshire, United Kingdom, HU3 2JZ
      • Recruiting
      • Hull & East Yorkshire NHS Trust
      • Principal Investigator: Shaji Sebastian, MD, MRCP, FRCP
      • Contact: Alison Talbot
• United States
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Recruiting
      • St. Joseph Mercy Hospital/Huron Gastroenterology Associates
      • Principal Investigator: Najm Soofi, MD, MPH
      • Contact: Aspen Bass
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mt Sinai Hospital
      • Contact: Sari Feldman
      • Principal Investigator: Jean-Frederic Colombel, MD
    • New York, New York, United States, 10065
      • Recruiting
      • New York-Presbyterian/Weill Cornell Medical Center
      • Contact: Fatiha Chabouni; Phone Number: 646-697-0985
      • Principal Investigator: Dana Lukin, MD
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Recruiting
      • Digestive Health Partners - Asheville Gastroenterology Associate
      • Principal Investigator: William Harlan, MD
      • Contact: Susan Westcott
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Atrium Health (Carolinas HealthCare)
      • Contact: Jessica Kearney-Bryan
      • Principal Investigator: Nilesh Lodhia, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Symptomatic remission; Treatment target defined as achievement of corticosteroid-free symptomatic remission.	Biological: 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.; Other Names: vedolizumab; 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.; Other Names: vedolizumab; 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.; Other Names: vedolizumab
Other: Symptomatic and endoscopic remission; Treatment target defined as achievement of corticosteroid-free symptomatic remission plus endoscopic remission.	Biological: 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.; Other Names: vedolizumab; 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.; Other Names: vedolizumab; 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.; Other Names: vedolizumab
Other: Symptomatic, endoscopic and histological remission; Treatment target defined as achievement of corticosteroid-free symptomatic remission plus endoscopic remission plus histological remission.	Biological: 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.; Other Names: vedolizumab; 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.; Other Names: vedolizumab; 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.; Other Names: vedolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Time to UC-related Complication Compared Between Treatment Target Groups 1 and 2.	Time to UC-related complication starting when a participant reaches their assigned treatment target, 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 Achieve Treatment Target	Time taken to achieve the respective targets among the randomized groups. Time will be censored for subjects who do not achieve their assigned target by Week 48.	up to 96 weeks
Fecal Calprotectin Levels	Change in fecal calprotectin levels from baseline to Weeks 8, 16, 32, 48, and 96.	Baseline, weeks 8, 16, 32, 48, and 96.
Difference in Time to UC-related Complication Compared Between Treatment Target Groups 2 and 3.	Time to UC-related complication starting when a participant reaches their assigned treatment target, 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	Time to UC-related complication compared between subgroups on and off corticosteroids at the time of achieving other relevant components of the treatment target.	From date of treatment target achievement until date of first UC-related complication until end of study (Week 96), whichever came first
C-Reactive Protein Concentration	Change in C-Reactive Protein concentration from baseline to Weeks 8, 16, 32, 48, 64, 80, and 96.	Baseline, weeks 8, 16, 32, 48, 64, 80, and 96
Difference in time to UC-related complication (as in the primary outcome and secondary outcomes 2 and 3)	Time to UC-related complication (as in the primary outcome and secondary outcomes 2 and 3) in the subgroup of subjects who exclusively reach their assigned target and not a higher target by Week 48.	Up to week 96
Evaluate the time to each type of UC-related complication	Evaluate, across the 3 target achievement groups, the time to each type of UC-related complication that comprises the primary endpoint.	Up to week 96
Assess the effect of treatment(s) on UC-related complications	Assess the effect of treatment(s) on UC-related complications that is mediated through treatment targets.	Up to week 96
Evaluate change in the UC-100 score from baseline to Weeks 16, 32, 48, and 96	To evaluate change in the UC-100 score from baseline to Weeks 16, 32, 48, and 96 (both in the full and the achieved-target populations). The UC-100 is a composite disease activity index consisting of clinical, endoscopic, and histological findings.The total UC-100 score ranges from 1 to 100, with higher scores representing more severe disease activity.	Up to week 96
Evaluate changes in the health-related quality of life (HRQoL) using the Inflammatory Bowel Disease Questionnaire (IBDQ)	To evaluate changes in the health-related quality of life (HRQoL) using the Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline to all follow-up visits.The Inflammatory Bowel Disease Questionnaire (IBDQ) includes 32 questions on 4 domains of health-related quality of life (HRQoL); the total score ranges from 32 and 224, with a higher score signifying a better outcome.	Up to week 96
Evaluate changes in the Work Productivity and Activity Impairment-UC (WPAI-UC) questionnaire	To evaluate changes in the Work Productivity and Activity Impairment-UC (WPAI-UC) questionnaire from baseline to all follow-up visits.The WPAI-UC (Work Productivity and Activity Impairment Questionnaire) consists of 6 questions that will grade the productivity while the participant is working on a scale from 0 to 10; a higher score signifies a higher impact on work productivity.	Up to week 96
Evaluate the change in Mayo Clinic Score (MCS; and subcomponents including the MES)	To evaluate the change in Mayo Clinic Score (MCS; and subcomponents including the MES) from baseline to Week 16,32,48 and 96/end of study (EOS). The Mayo Clinic Score for Ulcerative Colitis is a score that ranges from 0 to 12 with higher scores indicating worse severity. The score has four items (Stool Frequency, Rectal Bleeding, Mucosal appearance at endoscopy, Physician rating of disease activity) each rated from 0 to 3, where 3 means highest severity.	Up to week 96
Describe the change in Geboes scores from baseline to baseline to Week 16, 32, 48 and 96/end of study (EOS)	To describe the change in Geboes scores from baseline to baseline to Week 16, 32, 48 and 96/end of study (EOS). Geboes score is the most commonly used histological score in ulcerative colitis [UC] and is divided in 6 grades: architectural changes [grade 0], chronic inflammatory infiltrate [grade 1], lamina propria neutrophils and eosinophils [grade 2], neutrophils in epithelium [grade 3], crypt destruction [grade 4] and erosions or ulcerations [grade 5].	Up to week 96
Describe the change in RHI scores from baseline to all baseline to Week 16, 32, 48 and 96/end of study (EOS)	To describe the change in RHI scores from baseline to all baseline to Week 16, 32, 48 and 96/end of study (EOS). The Robarts Histopathology Index (RHI) is a validated instrument that measures histological disease activity in ulcerative colitis. The RHI assesses four characteristics of mucosal activity, inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration, all of which are rated on a scale of 0 to 3, with higher scores representing more severe disease activity.	Up to week 96
Describe the change in Nancy Histological Index scores from baseline to baseline to Week 16, 32, 48 and 96/end of study (EOS)	To describe the change in Nancy Histological Index scores from baseline to baseline to Week 16, 32, 48 and 96/end of study (EOS). The Nancy Histological Index is made up of 3 items: acute inflammatory cell infiltrates, chronic inflammatory cell infiltrates, and the presence of ulceration. Histological disease activity is graded on a 5-point scale; from grade 0 (no histologically significant disease) to grade 4 (severely active disease), with this grade being determined by the scoring algorithm.	Up to week 96
Evaluate the numbers of AEs and SAEs among the 3 randomized groups	To evaluate the numbers of AEs and SAEs among the 3 randomized groups.	Up to week 96
Validate the Symptoms and Impacts Questionnaire for UC (SIQ-UC) tool in English-fluent subjects	To validate the Symptoms and Impacts Questionnaire for Ulcerative Colitis (SIQ-UC) tool in English-fluent subjects. SIQ-UC consists of a symptom domain, which includes Gastrointestinal, pain and discomfort, nutrition-related, and fatigue-related symptoms; and an impact domain, which includes concepts related to daily activities, nutrition, emotional well-being, and productivity.	Up to week 96

Collaborators and Investigators

• Sponsor: Alimentiv Inc.
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Principal Investigator: Vipul Jairath, MD, Alimentiv Inc.

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2020
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: RP1706; 2019-002485-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes