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

Nantes University Hospital19 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

ULCERATIVE COLITIS

Interventions

VEDOLIZUMABDRUG

Infusion at week 0 week 2 week 6 week 14 for all patients Infusion at week 22 for responder patient only

ADALIMUMABDRUG

For nonresponder patients only : Injection at week 22 week 24 week 26 and week 28

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Chu Angers

Angers, France

Chd Vendee

La Roche-sur-Yon, France

Chu Nantes

Nantes, France

Chu Rennes

Rennes, France

Outcomes

Primary Outcomes

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.

Time frame: week 0

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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,

Time frame: week 22

Data from ClinicalTrials.gov

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