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

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.

Study Overview

• Status: Terminated
• Conditions: ULCERATIVE COLITIS
• Intervention / Treatment: Drug: VEDOLIZUMAB; Drug: ADALIMUMAB

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).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • La Roche Sur Yon, France
    • CHD Vendée
  • Nantes, France
    • Chu Nantes
  • Rennes, France
    • CHU Rennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VEDOLIZUMAB; 300 mg IV	Drug: VEDOLIZUMAB; Infusion at week 0 week 2 week 6 week 14 for all patients Infusion at week 22 for responder patient only; Other Names: entyvio; Drug: ADALIMUMAB; For nonresponder patients only : Injection at week 22 week 24 week 26 and week 28; Other Names: HUMIRA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Takeda; Mauna Kea Technologies

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2017
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 19, 2016
• First Posted (Estimate): August 25, 2016

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: biomarker; ULCERATIVE COLITIS; confocal endomicroscopy; vedolizumab,
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Adalimumab; Vedolizumab
• Other Study ID Numbers: RC15_0457

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO