Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)

Study Overview
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Brief Summary
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The main objective of this project is to demonstrate the feasability of an endomicroscopic biomarker of efficacy of vedolizumab and adalimumab, in Ulcerative colitis (UC) by coupling vedolizumab to a fluorescent component, FITC (Fluorescein isothiocyanate) , and adalimumab to rhodamine. This project should allow the development of a biomarker of therapeutic efficacy for vedolizumab and adalimumab that can be used in a single time-frame in vivo in humans, while respecting manufacturing standards and Good manufacturing procedures.

Detailed Description
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Patients will be recruited before initiation of vedolizumab injections. The schedule for vedolizumab infusions will corresponding to the protocol follow-up visits (Week 0, W2, W6, W14, W22), and flexible sigmoidoscopy appointments will be performed at Week 0 and 22. For responder patients, the end of the study will occured two weeks after the last vedolizumab infusion (W24). At week 22, nonresponder patients to vedolizumab may be treated by adalimumab in the absence of contraindication and depending on the decision of the physician responsible for the patient. Patients will be treated every two weeks during 8 weeks. The protocol follow up will end 2 weeks after the fourth adalimumab injection. During W0 and W22, colon biopsies will be collected. Blood samples will be collected on W0, W2, W6, W14, W22 (and W30 for non responder).

Official Title
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Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)

Conditions
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ULCERATIVE COLITIS

Intervention / Treatment
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* Drug: VEDOLIZUMAB
* Drug: ADALIMUMAB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with moderate to severe UC defined by an overall Mayo score ≥ 5 and an endoscopic sub-score ≥ 2 points and rectal bleeding score ≥ 1 point Extension > 15 cm from the anal margin Requiring treatment with biotherapy and meeting the indications for the treatment Affiliated with a social security scheme Exclusion Criteria: Crohn's disease or unclassified colitis Severe acute colitis Requirement for immediate surgical treatment Previous treatment with vedolizumab or anti-TNF-α Contraindication to the use of vedolizumab or an anti-TNF-α agent Contraindication to the use of adalimumab Corticosteroid therapy > 20 mg/day Corticosteroid therapy started within the previous two weeks Conventional Immunosppressor started within the previous month Colonic dysplasia or known cancer Likelihood to refuse two rectosigmoidoscopies, performed eighteen weeks apart Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 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<br>300 mg IV | Drug: VEDOLIZUMAB<br>* Infusion at week 0 week 2 week 6 week 14 for all patients Infusion at week 22 for responder patient only<br>* Other names: entyvio;Drug: ADALIMUMAB<br>* For nonresponder patients only : Injection at week 22 week 24 week 26 and week 28<br>* Other names: HUMIRA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate the feasibility of an ex vivo labeling of intestinal immune cells with a combination of two markers: vedolizumab-FITC and adalimumab-Alexa Fluor 647 | Presence of fluorescent cells by Cellvizio® examination field for each of the antibodies: FITCcoupled vedolizumab and Alexa Fluor 647-coupled adalimumab at week 0 for all the patients. | week 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantify, ex vivo, the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa of patients with moderate to severe UC that are associated with clinical remission at week 22 (W22) after the initiation of treatment with vedolizumab. | -Number of fluorescent cells by Cellvizio® examination field for each of the antibodies: FITC-coupled vedolizumab and Alexa Fluor 647-coupled adalimumab / Score of clinical response assessment | Week 22 | 
| Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of clinical response induced by treatment with a standard dose of vedolizumab | - Number of fluorescent cells / Mayo clinic sub-score | week 22 | 
| Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of endoscopic remission induced by treatment with a standard dose of vedolizumab | - Number of fluorescent cells / Geboes sub-score | week 22 | 
| Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of histologic remission induced by treatment with a standard dose of vedolizumab | - Number of fluorescent cells / Mayo endoscopic sub-score, | week 22 | 
| Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of clinical response induced by treatment with a standard dose of vedolizumab | - Number of fluorescent cells / rectal bleeding score | week 22 | 
| Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical response at w30 to adalimumab | Evolution of Number of fluorescent cells by Cellvizio® examination field for each of the antibodies between week 0 and week 22 / Mayo clinic sub-score | from week 0 to week 30 | 
| Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab | Evolution of Number of fluorescent cells by Cellvizio® examination field for each of the antibodies between week 0 and week 22 / Mayo endoscopic sub-score, | from week 0 to week 30 | 
| Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab | Evolution of Number of fluorescent cells by Cellvizio® examination field for each of the antibodies between week 0 and week 22 / Geboes sub-score | from week 0 to week 30 | 
| Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical remission at w30 to adalimumab | Evolution of Number of fluorescent cells by Cellvizio® examination field for each of the antibodies between week 0 and week 22 / rectal bleeding score | from week 0 to week 30 | 
| Compare the number of positive immune cells FITC-coupled vedolizumab in the intestinal mucosa of patients with UC | Average of Number of fluorescent cells FITC-coupled vedolizumab / patient | week 0 | 
| Compare the number of positive immune cells Alexa Fluor 647-coupled adalimumab in the intestinal mucosa of patients with UC | Average of Number of fluorescent cells Alexa Fluor 647-coupled adalimumab/ patient | week 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vedolizumab,, confocal endomicroscopy, biomarker, ULCERATIVE COLITIS