Determination of the Optimal Treatment Target in Ulcerative Colitis

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. 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:

* 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

Interventions

BIOLOGICAL

Treatment Algorithm A

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.

BIOLOGICAL

Treatment Algorithm B

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.

BIOLOGICAL

Treatment Algorithm C

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.

Sponsors & Collaborators

• Takeda Development Center Americas, Inc.

  collaborator INDUSTRY

• Alimentiv Inc.

  lead OTHER

Principal Investigators

• Vipul Jairath, MD · Alimentiv Inc.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-02-18

Primary Completion

2026-03-31

Completion

2026-03-31

FDA Drug

Yes

Countries

• United States
• Belarus
• Belgium
• Canada
• France
• Italy
• Netherlands
• Poland
• Ukraine
• United Kingdom

Study Locations