Ulcerative Colitis (UC) MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Trade Name: Entyvio
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: vedolizumab
CAS Number: 943609-66-3
Current Sponsor code: MLN0002
Other descriptive name: VEDOLIZUMAB
Con
Sponsors
Robarts Clinical Trials Inc.
Eligibility
Sex/Gender
All
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 histopathological 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 trials without investigational product may be permitted at the discretion of the investigator) 7. Willing to perform a standard of care tuberculosis (TB) test and hepatitis B and C test prior to starting any biologic drug during the study, 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 561 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 99
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 known C. difficile infection 8. Pregnant women 9. Subjects with hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required 10. Subjects who have active or latent TB. If a negative test results is available in the 12 months prior to randomization, retesting is not required 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: -Evaluate time to UC-related complication: - per (sub)group; - per (sub)group which reaches target and not higher by Week 48 -Evaluate if treatment to target of: - symptomatic + endoscopic remission (Group 2) is superior to symptomatic remission (Group 1); - corticosteroid-free symptomatic + endoscopic + histological remission (Group 3) is superior to corticosteroid-free symptomatic + endoscopic remission (Group 2) -Assess time to achieve respective target per randomized group -Assess effect of treatment allocation on UC-related complication -Evaluate change in: - fecal calprotectin/CRP/HRQoL/WPAI-UC from baseline to all follow-up visits per (sub)group; - UC-100/Mayo Clinic/ Geboes/RHI/NHI scores from baseline to Weeks 16/32/48/96 per (sub)group -Evaluate numbers of AEs and SAEs per (sub)group -Explore urine, stool, colonic mucosa, and blood samples for biomarkers and drug concentrations that are associated with clinically important outcomes -Validate SIQ-UC tool;Primary end point(s): Time to UC-related complication. ;Timepoint(s) of evaluation of this end point: Up to 80 weeks of follow-up after achieving target of corticosteroid-free symptomatic + endoscopic + histological remission. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to UC-related complications 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 + histologic 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 among the 3 randomized groups. 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 achieved-target populations) 7. The effect of treatment allocation on UC-related complication 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 | — |
Countries
Belarus, Belgium, Canada, France, Italy, Netherlands, Poland, Russian Federation, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Project Manager
Robarts Clinical Trials Inc.
Outcome results
None listed