Clinical trial NCT02878083: Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)
Official title: Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: ULCERATIVE COLITIS
Keywords: vedolizumab,
confocal endomicroscopy
biomarker
ULCERATIVE COLITIS
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Takeda
name: Mauna Kea Technologies
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2016-08-25
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: week 0
Secondary outcomes:
measure: 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.
timeFrame: Week 22
measure: 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
timeFrame: week 22
measure: 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
timeFrame: week 22
measure: 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
timeFrame: week 22
measure: 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
timeFrame: week 22
measure: Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical response at w30 to adalimumab
timeFrame: from week 0 to week 30
measure: Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab
timeFrame: from week 0 to week 30
measure: Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab
timeFrame: from week 0 to week 30
measure: Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical remission at w30 to adalimumab
timeFrame: from week 0 to week 30
measure: Compare the number of positive immune cells FITC-coupled vedolizumab in the intestinal mucosa of patients with UC
timeFrame: week 0
measure: Compare the number of positive immune cells Alexa Fluor 647-coupled adalimumab in the intestinal mucosa of patients with UC
timeFrame: week 0
Other outcomes:
Locations:
city: Angers
country: France
facility: Chu Angers
city: La Roche Sur Yon
country: France
facility: Chd Vendee
city: Nantes
country: France
facility: Chu Nantes
city: Rennes
country: France
facility: Chu Rennes
Study officials:
affiliation: Nantes University Hospital
name: ARNAUD BOURREILLE, MD-PHD
role: PRINCIPAL_INVESTIGATOR
References: