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

ULCERATIVE COLITIS Clinical Trial

— DETECT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02878083
• Other study ID #: RC15_0457
• Status: Terminated
• Phase: N/A
• Start date: January 11, 2017
• Est. completion date: January 1, 2021

Study information

• Verified date: February 2023
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: January 1, 2021
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-a

• Contraindication to the use of vedolizumab or an anti-TNF-a 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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• ULCERATIVE COLITIS

Intervention

Drug:
• VEDOLIZUMAB
Infusion at week 0 week 2 week 6 week 14 for all patients Infusion at week 22 for responder patient only
• ADALIMUMAB
For nonresponder patients only : Injection at week 22 week 24 week 26 and week 28

Locations

Country	Name	City	State
France	Chu Angers	Angers
France	Chd Vendee	La Roche Sur Yon
France	Chu Nantes	Nantes
France	Chu Rennes	Rennes

Sponsors (4)

Lead Sponsor	Collaborator
Nantes University Hospital	Institut National de la Santé Et de la Recherche Médicale, France, Mauna Kea Technologies, Takeda

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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