Colitis, UlcerativePhase 4VERDICTNCT04259138
Determination of the Optimal Treatment Target in Ulcerative Colitis
A Phase 4 study testing Treatment Algorithm A, Treatment Algorithm B and Treatment Algorithm C in people with Colitis, Ulcerative, run by Alimentiv Inc. at 58 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Treatment Algorithm A, Treatment Algorithm B and Treatment Algorithm C
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 672 participants
- Where
- 58 sitesin 10 countries
- Study dates
- 18 Feb 2020to 13 Apr 2026
- Phase
- Phase 4
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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).
Who cannot join
- 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.
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- 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.
- History of HIV or positive test at screening (Italy-specific criterion).
- Any other contraindication(s)to vedolizumab (Italy-specific criterion).
- 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.
- If male, the participant intends to donate sperm during the course of this study or for 18 weeks after the last dose.
- 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).
Trial locations and contacts
58 sites in 10 countries.
58 sites in 10 countries
Canada10 sites
Barrie GI Associates Inc.
Barrie, Ontario, L4M 7G1
University of Calgary
Calgary, Alberta, T2N 4Z6
McMaster University Medical Centre
Hamilton, Ontario, L8S 4L8
London Health Sciences Centre - University Campus
London, Ontario, N6A 5A5
LHSC - Victoria Hospital
London, Ontario, N6A 5W9
McGill University Health Centre (MUHC) Montreal General Hospital
Montreal, Quebec, H3G 1A4
ABP Research Services Corp.
Oakville, Ontario, L6L 5L7
Taunton Surgical Centre
Oshawa, Ontario, L1J 0C7
Toronto Immune and Digestive Health Institute (TIDHI)
Toronto, Ontario, M6A 3B4
GIRI (GI Research Institute)
Vancouver, British Columbia, V6Z 2K5
Poland8 sites
Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszcz
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168
Szpital Miejski Sw. Jana Pawla II w Elblagu
Elblag, 82300
Gabinet Endoskopii Przewodu Pokarmowego
Krakow, Lesser Poland Voivodeship, 31009
Oddział Gastroenterologiczny SP ZOZ w Łęcznej
Łęczna, 21-010
Endoskopia Sp. z.o.o.
Sopot, Pomeranian Voivodeship, 81-756
Sonomed Sp. z o.o. - Centrum Medyczne
Szczecin, West Pomeranian Voivodeship, 71-685
GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.
Torun, Kuyavian-Pomeranian Voivodeship, 87-100
WIP Warsaw IBD Point Profesor Kierkus
Warsaw, Masovian Voivodeship, 00-72
United Kingdom8 sites
University Hospitals Birmingham NHS Foundation Trust (UHB) - Queen Elizabeth Hospital Birmingham
Birmingham, West Midlands, B15 2GW
Russells Hall Hospital
Dudley, West Midlands, DY1 2HQ
Oxford University Hospitals NHS Foundation - John Radcliffe Hospital
Headington, Oxford, OX39DU
Hull & East Yorkshire NHS Trust
Hull, Yorkshire, HU3 2JZ
Barts Health NHS Trust / Whipps Cross University Hospital
Leytonstone, E11 1NR
Barts Health NHS Trust - Royal London Hospital
London, E1 1BB
University of Nottingham NHS Trust
Nottingham, NG7 2UH
Hampshire Hospitals NHS Foundation Trust - The Royal Hampshire County Hospital
Winchester, Hampshire, SO22 5DG
Ukraine7 sites
Dniepropetrovsk State Medical Academy
Dnipro
Odesa Regional Clinical Hospital
Odesa
Ternopil City Communal Emergency Medical Care Hosp
Ternopil
Uzhhorod National University
Uzhhorod
Vinnytsia City Clinical Hospital #1, Dept of Gastroenterology
Vinnytsia
Vinnytsia M.I. Pyrohov Regional Clinical Hospital
Vinnytsia
City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU
Zaporizhzhya, 69065
France6 sites
CHU Besançon - Hôpital Jean Minjoz
Besançon, Bourgogne-Franche-Comté, 25000
CHRU de Lille - Hopital Claude Huriez
Lille, Hauts-de-France, 59037
CHRU Montpellier - Hopital Saint Eloi
Montpellier, Occitanie, 34295
CHU de Bordeaux - Hopital Haut Leveque - Groupe Hospitalier Sud
Pessac, New Aquitaine, 33604
CH Saint Etienne Hopital Nord
Saint-Priest-en-Jarez, Auvergne-Rhône-Alpes, 42055
CHRU De Nancy - Hopital de Brabois
Vandœuvre-lès-Nancy, Grand Est, 54500
United States5 sites
Digestive Health Partners - Asheville Gastroenterology Associate
Asheville, North Carolina, 28801
Atrium Health (Carolinas HealthCare)
Charlotte, North Carolina, 28204
Icahn School of Medicine at Mt Sinai Hospital
New York, New York, 10029
New York-Presbyterian/Weill Cornell Medical Center
New York, New York, 10065
St. Joseph Mercy Hospital/Huron Gastroenterology Associates
Ypsilanti, Michigan, 48197
Italy5 sites
Azienda Ospedaliera - Polyclinico Sant'Orsola-Malpighi
Bologna, Emilia-Romagna, 40138
Ospedale San Raffaele S.r.I.
Milan, Milan, 20132
Azienda Ospedaliera di Padova
Padova, Padua, 35128
Policlinico Universitario Agostino Gemelli
Roma, Rome, 00-168
Istituto Clinico Humanitas
Rozzano, Milan, 20089
Netherlands4 sites
Amsterdam UMC - Academisch Medisch Centrum
Amsterdam, North Holland, 1081 HV
Catharina Hospital
Eindhoven, North Brabant, 5623 EJ
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6525 GA
ETZ Hospital Tilburg
Tilburg, North Brabant, 5022 GC
Belgium3 sites
Imelda Ziekenhuis Bonheiden
Bonheiden, Antwerp, 2820
University Hospital Ghent
Ghent, East Flanders, 9000
UZ Leuven - University Hospital Gasthuisberg
Leuven, Flemish Brabant, 3000
Belarus2 sites
Gomel Regional Clinical Hospital
Homyel, Homiel, 246029
Vitebsk Regional Clinical Hospital
Vitebsk, Vitebsk Oblast, 210037
About this study
Official title: 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:
Read more
- 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
- Being tested
- Treatment Algorithm A, Treatment Algorithm B, Treatment Algorithm C
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment Algorithm ABiological
Also called vedolizumab
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 BBiological
Also called vedolizumab
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 CBiological
Also called vedolizumab
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.
| Study group | Role | What they receive |
|---|---|---|
| Symptomatic remission | Other | Treatment target defined as achievement of corticosteroid-free symptomatic remission. Receives: 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. Receives: 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. Receives: Biological: Treatment Algorithm A; Biological: Treatment Algorithm B; Biological: Treatment Algorithm C |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Time to UC-related complication starting when a participant reaches their assigned treatment target, compared between treatment target groups 1 and 2.
Measured: 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.
Time to UC-related complication starting when a participant reaches their assigned treatment target, compared between treatment target groups 2 and 3.
Measured: 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.
Measured: 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.
Measured: up to 96 weeks
Fecal Calprotectin Levels
Change in fecal calprotectin levels from baseline to Weeks 8, 16, 32, 48, and 96.
Measured: Baseline, weeks 8, 16, 32, 48, and 96.
C-Reactive Protein Concentration
Change in C-Reactive Protein concentration from baseline to Weeks 8, 16, 32, 48, 64, 80, and 96.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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].
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start18 Feb 2020
- Primary completion13 Apr 2026
- Study completion13 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 672 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alimentiv Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Vipul Jairath, MD, Principal investigator, Alimentiv Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04259138
- Sponsor's protocol ID
- RP1706
- Other IDs
- 2019-002485-12, 2019
- Acronym
- VERDICT
- Status last verified
- Sep 2026
- First submitted
- 4 Feb 2020
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 38336367