Overview

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 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

Eligibility

Inclusion Criteria:

• Diagnosis of UC confirmed by clinical, endoscopic, and histopathological 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 subject 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 trials without investigational product may be permitted at the discretion of the investigator)
• 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
• 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
• 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

Exclusion Criteria:

• 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
• Current or previous treatment with vedolizumab, ertrolizumab, 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 screening
• Known diagnosis of CD, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis
• Short gut syndrome
• Positive stool culture for or active C. difficile infection (as demonstrated by positive toxin and/or antigen)
• Pregnant women
• 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
• 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
• 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 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)
• 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
• The subject has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization