Chronic inflammatory bowl disease Ulcerative colitis
Conditions
Interventions
Group 1 will be treated to a target of corticosteroid-free symptomatic remission
Group 2 will be treated to a target of corticosteroid-free endoscopic +
symptomatic remission
Group 3 will be treated
Sponsors
Alimentiv B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must meet each of the following criteria for enrollment into the study: 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 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 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 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. 11. Subjects who are not responding to their existing treatment for UC (Netherlands-specific criterion).
Exclusion criteria
Exclusion criteria: Subjects who exhibit any of the following conditions are ineligible for the study: 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 [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 Clostridiodes difficile infection 8. Pregnant women 9. Known hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required 10. Known active or latent TB. If a negative test results is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization. 11. Received any investigational drug within 30 days prior to enrollment/target assignment 12. 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, or any unstable or uncontrolled medical disorder) 13. 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 14. The subject has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization 15. Hypersensitivity to any excipient of vedolizumab 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 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. 19. If male, the subject 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. Time to UC-related complication starts from the point the subjects reach their assigned targets. The primary comparison is between subjects randomized to the treatment target of corticosteroid-free symptomatic + endoscopic + histological remission (Group 3) and subjects randomized to the treatment target of corticosteroid-free symptomatic remission (Group 1). UC-related complication is defined as any of the following: 1) hospitalization for treatment of a UC flare; 2) a colectomy for UC (defined as a colectomy for chronic active or acute severe colitis, but not primarily for dysplasia); 3) rescue therapy (such as new initiation or dose intensification of a corticosteroid, TNF antagonist, vedolizumab, tofacitinib, or ustekinumab) for a documented UC flare 4) UC treatment-related complication; or 5) other UC disease-related complication. Time will be censored for subjects lost to follow-up or for subjects who do not experience a UC-related complication at the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary outcome evaluations of the study will compare the treatment groups with regards to: 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. 6. Across the 3 randomized groups, time to each type of UC-related complication separately that comprises the primary endpoint 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. Ch | — |
Countries
Netherlands
Outcome results
None listed