Corticosteroids With Vedolizumab in Crohn's Disease

Study Overview
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Brief Summary
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Use of co-induction with corticosteroid therapies may accelerate the remission rate when used with vedolizumab. Further, this may lead to higher rates of response and remission at week 10 than would be seen with vedolizumab monotherapy.

Detailed Description
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This study will examine prednisone co-induction with vedolizumab in patients with Crohn's disease. To address questions regarding the effect of co-induction on mucosal healing, the study will include colonoscopic assessment of mucosal healing. Finally, colonic biopsies in this study will allow to elucidate further the mechanism of action of vedolizumab in Crohn's disease through immune phenotyping studies.

Official Title
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Corticosteroids as Co-Induction Agents With Vedolizumab in Crohn's Disease: a Double-blind Placebo Controlled Randomized Trial

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebo
* Drug: Vedolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at entry 18 to 70 CDAI score > 220 Concomitant azathioprine, methotrexate, or mercaptopurine permitted if dose has been stable for > 8 weeks. Prior anti-TNFα antibody use permitted but must be discontinued (>2 weeks from last dose) prior to initiation of vedolizumab. Documented ulceration on colonoscopy done at screening of 3 or more large ulcers or 10 or more aphthous ulcers Able to provide written informed consent. Patient is planned for or eligible to initiate vedolizumab Exclusion Criteria: Concurrent use of anti-TNFα antibodies. No corticosteroids within prior 3 months (other than budesonide controlled ileal release) No stoma at the time of enrollment No absolute contraindication to systemic corticosteroid use such as hypersensitivity to any part of the formulation, systemic fungal infection, or recent administration of live or live attenuated vaccine within prior two weeks. Pregnant women or plans for pregnancy within 3 months of study inclusion Presence of stoma, more than three small-bowel resections, or documented history of short bowel syndrome Intestinal stricture requiring surgery Abdominal abscess Inability or unwillingness to provide informed consent Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prednisone co-inductive therapy<br>Prednisone 40 mg/day starting at week 0 for 2 weeks, tapered by 10 mg weekly to achieve 0 mg by end of week 5 | Drug: Prednisone<br> <br> * Other names: corticosteroids;Drug: Vedolizumab<br>* 300mg IV over 30 minutes. Both arms will receive vedolizumab at weeks 0, 2, and 6.<br>* Other names: Entyvio;|
| Placebo Comparator: Placebo<br>Identical placebo taper | Drug: Placebo<br> <br> Drug: Vedolizumab<br>* 300mg IV over 30 minutes. Both arms will receive vedolizumab at weeks 0, 2, and 6.<br>* Other names: Entyvio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crohn's Disease Activity Index (CDAI) | Clinical remission, defined as CDAI < 150, in group with steroid co-induction vs. placebo co-induction. The purpose of this crohn's disease activity index (CDAI) calculator is to gauge the progress or lack of progress for people with crohn's disease. CDAI scores below 150 indicate a better prognosis than higher scores | baseline, week 6, week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) | The SES-CD tool is used to quantify and compare inflammatory load. The Simple Endoscopic Score for Crohn Disease (SES-CD) assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each item is scored from 0-3, with total score from 0-60. Higher score indicates more severe endoscopic activity. | baseline and week 10 | 
| Change in C-Reactive Protein (CRP) | Comparison of absolute change in CRP from baseline to week 10. C-reactive protein is produced by the liver. The level of CRP rises when there is inflammation throughout the body. | baseline and week 10 | 
| Change in Calprotectin | Comparison of absolute change in calprotectin from baseline to week 6. Calprotectin is a stool (fecal) test that is used to detect inflammation in the intestines. | baseline, week 6 and week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vedolizumab, Corticosteroids, Prednisone, Crohn's disease