An Open Label Single-arm Phase 4 Study of Vedolizumab in Subjects With Newly Diagnosed Active Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this research study is to determine whether starting the drug vedolizumab earlier than its FDA approved use can lead to better control of UC then using older drugs that we have historically used to treat UC. Vedolizumab is FDA-approved to be used after initial Corticosteroid treatments have failed or other UC treatments have failed. We will study if using vedolizumab as an early treatment for your UC will allow you to get off corticosteroids and prevent UC from worsening and requiring surgery. Vedolizumab is given intravenously initially every 2 weeks and then every 8 weeks.

Detailed Description
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Based upon our published data, 53% of patients who require CS at the time of diagnosis of UC will be in CS free remission in the absence of colectomy by the end of 52 weeks. Early corticosteroids requirement after the diagnosis of ulcerative colitis diagnosis can predict a more severe long-term course of the disease. This work formed the basis of this research project. We had postulated that patients requiring steroids early in the course of their disease had worse prognosis than those who did not and should be treated more aggressively early in the course of their disease to prevent future complications like colectomy. The current standard of care for treatment of UC in the VA is as follows: At the time of diagnosis all the patients are started on a 5-ASA compound. Those patients who have very severe disease are concomitantly started on steroids. If they are very sick they are concomitantly started on an anti-TNF compound also with the goal of tapering them off steroids. Based upon response to therapy medications are adjusted. If there is no relief with 5-ASA compounds they can be started on steroids. For those on steroids and who cannot be weaned off steroids or are requiring multiple courses of steroids, they will have their therapy advanced to an anti-TNF or vedoluzimab. For those failing an anti-TNF they can be shifted to vedoluzimab. Thus, at the VA, vedoluzimab is available at the VA thru the non-formulary process. It is restricted to GI as 3rd line agent for UC. That is, it is used after oral agents fail and after anti-TNF agents (Humira® or Remicade®). The indications for Vedoluzimab use in the VA are as follows with regard to failure: The patient has had adequate therapeutic trials of ONE of the following treatments, unless the patient has a contraindication, risk factor for serious adverse event*, or intolerance to the agent(s): Criterion 1 is an option with or without therapeutic drug monitoring.) A TNFI and an antimetabolite immunomodulator, separately or in combination. OR An initial and second TNFI, if therapeutic drug monitoring after secondary nonresponse to TNFI therapy indicates high titers of anti-TNFI antibodies. OR A TNFI, when either of the following apply: Induction therapy with an agent from a different biologic class is needed to treat an inadequate response (with confirmed active inflammation / persistent disease) following TNFI induction therapy (i.e., primary nonresponse) and therapeutic drug monitoring shows therapeutic or high trough TNFI serum concentrations. The patient lost response (i.e., secondary nonresponse not due to adverse reaction) to the initial TNFI in association with therapeutic or high trough TNFI serum concentration.

Official Title
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An Open Label Single-arm Phase 4 Study of Vedolizumab in Subjects With Newly Diagnosed Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Vedolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed active ulcerative colitis, defined as a Mayo Clinic score of 6 to 12 Prior Sigmoidoscopy sub score of at least 2, and disease that extended 15 cm or more from the anal verge Must have required CS for treatment of their symptoms within 2 weeks of diagnosis and have not reached symptom adequate response and they still have moderate to severe disease, indicated by a Mayo score 6 - 12 In subjects that enroll and are eligible to continue in the study, study drug needs to be started within 3 months of the subject starting corticosteroids Exclusion Criteria: Currently treated with either anti-TNF therapy, immunomodulators or methotrexate due to the severity of their condition, making them not appropriate for vedolizumab Toxic megacolon, abdominal abscess, symptomatic colonic stricture, an increased risk of infectious complications An anticipated requirement for major surgery, colonic dysplasia or adenomas and malignant neoplasms Neurological disorders Pregnant or lactating females Clinical response to steroids prior to starting study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vedolizumab 300mg<br>vedolizumab open label | Drug: Vedolizumab<br>* Initiation: 300 mg at week 0, 2 and 6. Maintenance: Every 8 weeks after the sixth week at a fixed dose of 300 mg<br>* Other names: entyvio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corticosteroid free remission as well as the absence of a colectomy | corticosteroid free remission as well as the absence of a colectomy | 52 weeks |