Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT) (DETECT)
Primary Purpose
ULCERATIVE COLITIS
Status
Terminated
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
VEDOLIZUMAB
ADALIMUMAB
Sponsored by
About this trial
This is an interventional treatment trial for ULCERATIVE COLITIS focused on measuring vedolizumab,, confocal endomicroscopy, biomarker, ULCERATIVE COLITIS
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
Sites / Locations
- Chu Angers
- Chd Vendee
- Chu Nantes
- Chu Rennes
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VEDOLIZUMAB
Arm Description
300 mg IV
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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
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,
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
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
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,
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
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
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
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
Full Information
NCT ID
NCT02878083
First Posted
August 16, 2016
Last Updated
February 16, 2023
Sponsor
Nantes University Hospital
Collaborators
Takeda, Mauna Kea Technologies, Institut National de la Santé Et de la Recherche Médicale, France
1. Study Identification
Unique Protocol Identification Number
NCT02878083
Brief Title
Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)
Acronym
DETECT
Official Title
Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
the CELLVIZIO device required to analyse biopsy is available until september 2020
Study Start Date
January 11, 2017 (Actual)
Primary Completion Date
January 2020 (Actual)
Study Completion Date
January 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital
Collaborators
Takeda, Mauna Kea Technologies, Institut National de la Santé Et de la Recherche Médicale, France
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ULCERATIVE COLITIS
Keywords
vedolizumab,, confocal endomicroscopy, biomarker, ULCERATIVE COLITIS
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VEDOLIZUMAB
Arm Type
Experimental
Arm Description
300 mg IV
Intervention Type
Drug
Intervention Name(s)
VEDOLIZUMAB
Other Intervention Name(s)
entyvio
Intervention Description
Infusion at week 0 week 2 week 6 week 14 for all patients Infusion at week 22 for responder patient only
Intervention Type
Drug
Intervention Name(s)
ADALIMUMAB
Other Intervention Name(s)
HUMIRA
Intervention Description
For nonresponder patients only : Injection at week 22 week 24 week 26 and week 28
Primary Outcome Measure Information:
Title
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
Description
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 Outcome Measure Information:
Title
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.
Description
-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
Title
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
Description
- Number of fluorescent cells / Mayo clinic sub-score
Time Frame
week 22
Title
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
Description
- Number of fluorescent cells / Geboes sub-score
Time Frame
week 22
Title
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
Description
- Number of fluorescent cells / Mayo endoscopic sub-score,
Time Frame
week 22
Title
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
Description
- Number of fluorescent cells / rectal bleeding score
Time Frame
week 22
Title
Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical response at w30 to adalimumab
Description
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
Time Frame
from week 0 to week 30
Title
Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab
Description
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,
Time Frame
from week 0 to week 30
Title
Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab
Description
Evolution of Number of fluorescent cells by Cellvizio® examination field for each of the antibodies between week 0 and week 22 / Geboes sub-score
Time Frame
from week 0 to week 30
Title
Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical remission at w30 to adalimumab
Description
Evolution of Number of fluorescent cells by Cellvizio® examination field for each of the antibodies between week 0 and week 22 / rectal bleeding score
Time Frame
from week 0 to week 30
Title
Compare the number of positive immune cells FITC-coupled vedolizumab in the intestinal mucosa of patients with UC
Description
Average of Number of fluorescent cells FITC-coupled vedolizumab / patient
Time Frame
week 0
Title
Compare the number of positive immune cells Alexa Fluor 647-coupled adalimumab in the intestinal mucosa of patients with UC
Description
Average of Number of fluorescent cells Alexa Fluor 647-coupled adalimumab/ patient
Time Frame
week 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ARNAUD BOURREILLE, MD-PHD
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chu Angers
City
Angers
Country
France
Facility Name
Chd Vendee
City
La Roche Sur Yon
Country
France
Facility Name
Chu Nantes
City
Nantes
Country
France
Facility Name
Chu Rennes
City
Rennes
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)
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