VERDICT - Optimal Treatment Target in Active Ulcerative Colitis (UC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alimentiv Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

15 Jan 2021 → 3 Apr 2026

Decision date (initial)

2024-09-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2024-514183-21-00

EudraCT number

2019-002485-12

ClinicalTrials.gov

NCT04259138

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Others

The primary objective of this trial is to determine whether, in subjects with moderately to severely active UC, treating to achieve a target of corticosteroid-free symptomatic + endoscopic + histological remission is superior to a treatment target of corticosteroid-free symptomatic remission, with regards to a primary endpoint of time to UC-related complication within up to 80 weeks of follow-up after achieving target.

Secondary objectives 19

1. To evaluate time to UC-related complication in the full analysis set, including subgroups on and off corticosteroids at the time of achieving other relevant components of the treatment target
2. To evaluate whether treatment to the target of symptomatic + endoscopic remission (Group 2) is superior to a treatment target of symptomatic remission (Group 1) in terms of the primary endpoint (both in the full and the achieved-target populations)
3. To evaluate whether treatment to the target of corticosteroid-free symptomatic + endoscopic + histological remission (Group 3) is superior to a treatment target of corticosteroid-free symptomatic + endoscopic remission (Group 2) in terms of the primary endpoint (both in the full and the achieved-target populations)
4. To evaluate 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
5. To assess the time taken to achieve the respective targets among the randomized groups. Time will be censored for subjects who do not achieved their assigned target by Week 48
6. To evaluate, across the 3 target achievement groups, the time to each type of UC-related complication that comprises the primary endpoint
7. To assess the effect of treatment(s) on UC-related complications that is mediated through treatment targets
8. To evaluate the change in fecal calprotectin levels from baseline to all follow-up visits
9. To evaluate the change in C-reactive protein (CRP) concentration from baseline to all follow-up visits
10. 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)
11. 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
12. To evaluate changes in the Work Productivity and Activity Impairment-UC (WPAI-UC) questionnaire from baseline to all follow-up visits
13. To evaluate the change in Mayo Clinic Score (MCS; and subcomponents including the MES) from baseline to Visits 4, 5, 6, and 9/end of study (EOS)
14. To describe the change in Geboes scores from baseline to baseline to Visits 4, 5, 6, and 9/EOS
15. To describe the change in RHI scores from baseline to all baseline to Visits 4, 5, 6, and 9/EOS
16. To describe the change in Nancy Histological Index scores from baseline to baseline to Visits 4, 5, 6, and 9/EOS
17. To evaluate the numbers of AEs and SAEs among the 3 randomized groups
18. To explore urine, stool, colonic mucosa, and serum samples for biomarkers and drug concentrations that are associated with clinically important outcomes
19. To validate the Symptoms and Impacts Questionnaire for UC (SIQ-UC) tool in English-fluent subjects

Conditions and MedDRA coding

Ulcerative colitis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 Mayo endoscopic subscore (MES) ≥ 2, with a minimum disease extent of 15 cm and objective evidence of inflammation that can be visualized using a central endoscopic imaging system.
4. Ability of subject 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 investigation trial for the duration of this trial (observational 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 subject 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 subject 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.

Exclusion criteria 18

1. Subjects 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) use within 2 weeks prior to screening endoscopy.
4. Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of >30 mg of prednisone or equivalent at randomization.
5. Known diagnosis of Crohn’s disease, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
6. Short gut syndrome.
7. Positive stool culture 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 subject’s ability to participate fully in the study or would compromise subject safety (such as history of malignancies, major neurological disorders, any unstable or uncontrolled medical disorder).
12. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the subject’s ability to comply with the study procedures.
13. The subject 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. If female, the subject 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.
17. If male, the subject intends to donate sperm during the course of this study or for 18 weeks after the last dose.
18. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy evaluation is time to UC-related complication according to the achieved-target population, defined by the subset who met their assigned treatment targets.

Secondary endpoints 19

1. Time to UC-related complication in the full analysis set, including subgroups on and off corticosteroids at the time of achieving other relevant components of the treatment target
2. Whether treatment to the target of symptomatic + endoscopic remission (Group 2) is superior to a treatment target of symptomatic remission (Group 1) in terms of the primary endpoint (both in the full and the achieved-target populations)
3. Whether treatment to the target of corticosteroid-free symptomatic + endoscopic + histological remission (Group 3) is superior to a treatment target of corticosteroid-free symptomatic + endoscopic remission (Group 2) in terms of the primary endpoint (both in the full and the achieved-target populations)
4. 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
5. Time taken to achieve the respective targets in each group. Time will be censored for subjects who do not achieve their assigned target by Week 48
6. Across the 3 randomized groups, time to each type of UC-related complication separately that comprises the primary endpoint (both in the full and the achieved-target populations)
7. The effect of treatment(s) on UC-related complications that is mediated through treatment targets
8. Change in fecal calprotectin levels from baseline to Weeks 8, 16, 32, 48, and 96 (both in the full and the achieved-target populations)
9. Change in C-reactive protein (CRP) concentration from baseline to Weeks 8, 16, 32, 48, 64, 80, and 96 (both in the full and the achieved-target populations)
10. Change in the UC-100 score from baseline to Weeks 16, 32, 48, and 96 (both in the full and the achieved-target populations)
11. Change in health-related quality of life (HRQoL) using the Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline to Weeks 16, 32, 48, 64, 80, and 96 (both in the full and the achieved-target populations)
12. Change in the Work Productivity and Activity Impairment-UC (WPAI-UC) questionnaire from baseline to Weeks 16, 32, 48, 64, 80, and 96 (both in the full and the achieved-target populations)
13. Change in Mayo Clinic Score (MCS; and subcomponents including the MES) from baseline to Weeks 16, 32, 48, and 96 (both in the full and the achieved-target populations)
14. Change in Geboes score from baseline to Weeks 16, 32, 48, and 96 (both in the full and the achieved-target populations)
15. Change in Robarts Histopathology Index (RHI) scores from baseline to Weeks 16, 32, 48, and 96 (both in the full and the achieved-target populations)
16. Change in Nancy Histological Index scores from baseline to Weeks 16, 32, 48, and 96 (both in the full and the achieved-target populations)
17. The numbers of adverse events (AEs) and serious AEs among the 3 randomized groups
18. Evaluation of urine, stool, colonic mucosa, and serum samples for biomarkers and drug concentrations that are associated with clinically important outcomes
19. Validation of the Symptoms and Impacts Questionnaire for UC (SIQ-UC) tool in English-fluent subjects

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alimentiv Inc.

Sponsor organisation

Alimentiv Inc.

Address

100 Dundas Street Suite 200

City

London

Postcode

N6A 5B6

Country

Canada

Scientific contact point

Organisation

Alimentiv Inc.

Contact name

PM Group

Public contact point

Organisation

Alimentiv Inc.

Contact name

PM Group

Third parties 4

Locations

5 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications