Back to resultsValue of Pharmacokinetic Assays in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease (VEDO-PREDIRESP)
Primary Purpose
Crohn Disease
Status
Terminated
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Vedolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Crohn Disease focused on measuring Crohn's disease, Vedolizumab, TNF (Tumor Necrosis Factor), Clinical response, Clinical remission
Eligibility Criteria
Inclusion Criteria :
- Aged over 18 years
- Men or non-pregnant women
- Patients with a diagnosis of Crohn's disease who requires to start Vedolizumab
- Crohn's disease defined as a Crohn's disease Activity Index (CDAI) > 150 points and/or fecal calprotectin levels > 250 µg/g of stool
- Crohn's Disease patients with previous failure with TNF (Tumor Necrosis Factor) antagonist agents and unacceptable side-effects from steroids, and/or immunosuppressive agents (i.e., azathioprine, 6-mercaptopurine, or methotrexate). In France, Vedolizumab has to be prescribed only in patients in failure or intolerant to anti-TNF.
- Patient taking corticosteroids orally, concomitant immunosuppressive agents, mesalamine, and antibiotics are allowed at stable dose for at least three months before inclusion. Steroid tapering has to be set up at Week 10 after starting Vedolizumab, according to the European Crohn and Colitis Organisation (ECCO) recommendations with a progressive decrease of steroids of 5 mg/day every week until complete withdrawn.
- Informed written consent given.
Exclusion Criteria:
- Existing pregnancy, lactation, or intended pregnancy within the next 15 months
- Minors or History of disease, including mental/emotional disorder that might interfere with their participation in the study
- Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
- Inability to comply with the protocol requirements
- Inability to fill in the diary cards during the last 7 days before each visit
- Presence of an ileo-/colonic stoma
- Patients with known colonic stricture and exclusive or predominant anal or perineal Crohn's disease lesions
- Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years)
- Short bowel syndrome
- Previous treatments with natalizumab, efalizumab or rituximab.
- Prior extensive colonic resection, obstructive (symptomatic) intestinal stricture, abdominal abscess, active or latent tuberculosis,
- Documented Clostridium difficile superinfection;
- Indeterminate colitis
- Concomitant leukocyte apheresis.
- Any contraindication to vedolizumab therapy
- Patients who denied the protocol, not ability to accept or sign consent of the protocol
- Subject involved in another interventional clinical trial
Sites / Locations
- CHU Kremlin Bicetre
- CHU d'Amiens
- CHU L'Archet
- CHU Lyon-Sud, Hospices Civils de Lyon, PIERRE-BENITE
- Chu Saint Etienne
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Crohn's disease patients
Arm Description
The patients will receive vedolizumab in compliance with the marketing authorization regimen (300 mg at weeks 0, 2, 6 and then every 8 weeks) in Crohn's Disease patients in clinical failure or intolerant to anti-TNF (Tumor Necrosis Factor) drugs. In case of lack of clinical response at week 10 or loss of response in the follow-up, all patients will be optimized with vedolizumab 300 mg at week 10 (additional infusion) and every following 4 weeks in contrast with responder patients at week 10 who will not have vedolizumab infusion at this time-point but will receive the next vedolizumab infusion at week 14 and then every 8 weeks, as recommended.
Outcomes
Primary Outcome Measures
Vedolizumab concentration at week 6
The primary objective is to determine the optimal threshold of Vedolizumab serum concentration measured at week 6 capable to predict the clinical response at week 10 with Vedolizumab.
Secondary Outcome Measures
Vedolizumab concentration at week 14
Determine the optimal threshold of Vedolizumab serum concentration measured at week 14 capable to predict the clinical remission at week 54 with Vedolizumab.
Concentration of Vedolizumab at week 2
Investigating whether the Vedolizumab concentrations measured at week 2 are predictive of a clinical response and clinical remission at week 10.
Presence of specific antibodies (anti-integrins) at week 2
Investigating whether the presence of specific antibodies (anti-integrins) measured at week 2 are predictive of a clinical response and clinical remission at week 10.
Concentration of Vedolizumab at week 14
Investigating whether the Vedolizumab concentrations measured at week 14 are predictive of a clinical response and clinical remission at week 54.
Presence of specific antibodies (anti-integrins) at week 14
Investigating whether the presence of specific antibodies (anti-integrins) measured at week 14 are predictive of a clinical response and clinical remission at week 54.
Vedolizumab and calprotectin levels at week 2
Analyzing the value of Vedolizumab trough levels measured at week 2 to predict a subsequent normalization of fecal calprotectin levels (< 250 micro grams/gram of stools) at week 10 under induction therapy with Vedolizumab in Crohn's Disease.
Vedolizumab and calprotectin levels at week 14
Analyzing the value of Vedolizumab trough levels measured at week 14 to predict a subsequent normalization of fecal calprotectin levels (< 250 micro grams/gram of stools) at week 54 under maintenance therapy with Vedolizumab in Crohn's Disease.
Intra and inter-individual heterogeneity of Vedolizumab levels
Investigating the intra and inter-individual heterogeneity of Vedolizumab levels within the time-course of Vedolizumab therapy, including the induction and maintenance phases. The dosage of Vedolizumab in patients blood will be used.
Proportion of loss of clinical response
Comparing the proportion of loss of clinical response in responder Crohn's Disease patients as well as in primary non-responders requiring Vedolizumab dose-intensification within one-year of follow-up.
Vedolizumab serum levels
Comparing the Vedolizumab serum levels prior and after Vedolizumab optimization in primary non-responder patients or experiencing a loss of response (secondary non-response) requiring additional infusions of Vedolizumab.
Concentration of Vedolizumab at week 54
Comparing the level of Vedolizumab between patients achieving a clinical remission or not at week 54.
Specific antibodies (anti-integrins) level at week 54
Comparing the specific antibodies (anti-integrins) levels between patients achieving a clinical remission or not at week 54.
Full Information
NCT ID
NCT02768532
First Posted
May 2, 2016
Last Updated
June 13, 2023
Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Theradiag, Takeda
1. Study Identification
Unique Protocol Identification Number
NCT02768532
Brief Title
Value of Pharmacokinetic Assays in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease
Acronym
VEDO-PREDIRESP
Official Title
VEDO-PREDIRESP Project: Value of Pharmacokinetic Assays (Vedolizumab and Anti-vedolizumab Antibody) in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
low inclusion rates
Study Start Date
July 1, 2016 (Actual)
Primary Completion Date
January 11, 2022 (Actual)
Study Completion Date
January 23, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Theradiag, Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Vedolizumab (VDZ) is a monoclonal antibody which has shown its efficacy in Crohn's disease by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Crohn's disease in patients in failure with anti-TNF (Tumor Necrosis Factor) agents.
For Crohn's disease patients treated with vedolizumab, a strong association between vedolizumab serum levels and clinical response to induction and maintenance was demonstrated by anterior studies.
It could be of paramount interest to early identify Crohn's Disease patients under vedolizumab who will be responders to vedolizumab induction and to identify those who will achieve clinical remission under maintenance therapy with vedolizumab.
Researchers decided to assess the clinical response to vedolizumab induction at week 10. For clinically non-responders at week 10, an additional dose of 300 mg of vedolizumab will be infused at week 10 and then every four weeks.
Detailed Description
Vedolizumab (VDZ) is a monoclonal antibody that binds to the heterodimer alpha 4 beta 7 integrin and which has shown its efficacy in Crohn's disease by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Crohn's disease in patients in failure with anti-TNF (Tumor Necrosis Factor) agents.
For Crohn's disease patients treated with vedolizumab, a strong association between vedolizumab serum levels and clinical response to induction and maintenance was demonstrated by anterior studies.
It could be of paramount interest to early identify Crohn's Disease patients under vedolizumab who will be responders to vedolizumab induction and to identify those who will achieve clinical remission under maintenance therapy with vedolizumab.
Researchers decided to assess the clinical response to vedolizumab induction at week 10, as the Gemini III trial has reported, among patients who had experienced previous TNF (Tumor Necrosis Factor) antagonist failure. 15% of those given vedolizumab were in remission at week 6 (P=0.433) versus 12% under placebo. At week 10, 26% under vedolizumab were in remission versus 12% in the placebo arm.
Moreover, at week 10, the proportion of patients presenting a clinical response was significantly higher in Crohn's Disease patients treated with vedolizumab (46% vs 24%).
In this study, for clinically non-responders at week 10, an additional dose of 300 mg of vedolizumab will be infused at week 10 and then every four weeks. In a post hoc analysis of GEMINI 2, additional dose of vedolizumab in patients clinically non responders to vedolizumab obtained a clinical remission in 33% of case.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
Keywords
Crohn's disease, Vedolizumab, TNF (Tumor Necrosis Factor), Clinical response, Clinical remission
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Crohn's disease patients
Arm Type
Experimental
Arm Description
The patients will receive vedolizumab in compliance with the marketing authorization regimen (300 mg at weeks 0, 2, 6 and then every 8 weeks) in Crohn's Disease patients in clinical failure or intolerant to anti-TNF (Tumor Necrosis Factor) drugs. In case of lack of clinical response at week 10 or loss of response in the follow-up, all patients will be optimized with vedolizumab 300 mg at week 10 (additional infusion) and every following 4 weeks in contrast with responder patients at week 10 who will not have vedolizumab infusion at this time-point but will receive the next vedolizumab infusion at week 14 and then every 8 weeks, as recommended.
Intervention Type
Drug
Intervention Name(s)
Vedolizumab
Other Intervention Name(s)
Entyvio
Intervention Description
During each 8 visits (screening, V0, V1, V2, V3, V4, V5, V6) at weeks-1, 0, 2, 6, 10, 14, 22, 54, respectively), the following parameters will be systematically recorded: Crohn's disease Activity Index (CDAI), adverse events.
Blood and fecal samples will be systematically collected at weeks 0, 2, 6, 10, 14, 22 and 54 for routine serum ultrasensitive CRP (C-Reactive Protein) and fecal calprotectin assessments and for vedolizumab pharmacokinetic parameters, including the vedolizumab trough levels and the specific anti-Vedolizumab antibodies. In case of loss of response, an additional measurement of serum CRP (C-Reactive Protein), fecal calprotectin and Vedolizumab pharmacologic parameters will be performed.
Primary Outcome Measure Information:
Title
Vedolizumab concentration at week 6
Description
The primary objective is to determine the optimal threshold of Vedolizumab serum concentration measured at week 6 capable to predict the clinical response at week 10 with Vedolizumab.
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
Vedolizumab concentration at week 14
Description
Determine the optimal threshold of Vedolizumab serum concentration measured at week 14 capable to predict the clinical remission at week 54 with Vedolizumab.
Time Frame
Week 14
Title
Concentration of Vedolizumab at week 2
Description
Investigating whether the Vedolizumab concentrations measured at week 2 are predictive of a clinical response and clinical remission at week 10.
Time Frame
Week 2
Title
Presence of specific antibodies (anti-integrins) at week 2
Description
Investigating whether the presence of specific antibodies (anti-integrins) measured at week 2 are predictive of a clinical response and clinical remission at week 10.
Time Frame
Week 2
Title
Concentration of Vedolizumab at week 14
Description
Investigating whether the Vedolizumab concentrations measured at week 14 are predictive of a clinical response and clinical remission at week 54.
Time Frame
Week 14
Title
Presence of specific antibodies (anti-integrins) at week 14
Description
Investigating whether the presence of specific antibodies (anti-integrins) measured at week 14 are predictive of a clinical response and clinical remission at week 54.
Time Frame
Week 14
Title
Vedolizumab and calprotectin levels at week 2
Description
Analyzing the value of Vedolizumab trough levels measured at week 2 to predict a subsequent normalization of fecal calprotectin levels (< 250 micro grams/gram of stools) at week 10 under induction therapy with Vedolizumab in Crohn's Disease.
Time Frame
Week 2
Title
Vedolizumab and calprotectin levels at week 14
Description
Analyzing the value of Vedolizumab trough levels measured at week 14 to predict a subsequent normalization of fecal calprotectin levels (< 250 micro grams/gram of stools) at week 54 under maintenance therapy with Vedolizumab in Crohn's Disease.
Time Frame
Week 14
Title
Intra and inter-individual heterogeneity of Vedolizumab levels
Description
Investigating the intra and inter-individual heterogeneity of Vedolizumab levels within the time-course of Vedolizumab therapy, including the induction and maintenance phases. The dosage of Vedolizumab in patients blood will be used.
Time Frame
Week 54
Title
Proportion of loss of clinical response
Description
Comparing the proportion of loss of clinical response in responder Crohn's Disease patients as well as in primary non-responders requiring Vedolizumab dose-intensification within one-year of follow-up.
Time Frame
Week 54
Title
Vedolizumab serum levels
Description
Comparing the Vedolizumab serum levels prior and after Vedolizumab optimization in primary non-responder patients or experiencing a loss of response (secondary non-response) requiring additional infusions of Vedolizumab.
Time Frame
Week 54
Title
Concentration of Vedolizumab at week 54
Description
Comparing the level of Vedolizumab between patients achieving a clinical remission or not at week 54.
Time Frame
Week 54
Title
Specific antibodies (anti-integrins) level at week 54
Description
Comparing the specific antibodies (anti-integrins) levels between patients achieving a clinical remission or not at week 54.
Time Frame
Week 54
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria :
Aged over 18 years
Men or non-pregnant women
Patients with a diagnosis of Crohn's disease who requires to start Vedolizumab
Crohn's disease defined as a Crohn's disease Activity Index (CDAI) > 150 points and/or fecal calprotectin levels > 250 µg/g of stool
Crohn's Disease patients with previous failure with TNF (Tumor Necrosis Factor) antagonist agents and unacceptable side-effects from steroids, and/or immunosuppressive agents (i.e., azathioprine, 6-mercaptopurine, or methotrexate). In France, Vedolizumab has to be prescribed only in patients in failure or intolerant to anti-TNF.
Patient taking corticosteroids orally, concomitant immunosuppressive agents, mesalamine, and antibiotics are allowed at stable dose for at least three months before inclusion. Steroid tapering has to be set up at Week 10 after starting Vedolizumab, according to the European Crohn and Colitis Organisation (ECCO) recommendations with a progressive decrease of steroids of 5 mg/day every week until complete withdrawn.
Informed written consent given.
Exclusion Criteria:
Existing pregnancy, lactation, or intended pregnancy within the next 15 months
Minors or History of disease, including mental/emotional disorder that might interfere with their participation in the study
Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
Inability to comply with the protocol requirements
Inability to fill in the diary cards during the last 7 days before each visit
Presence of an ileo-/colonic stoma
Patients with known colonic stricture and exclusive or predominant anal or perineal Crohn's disease lesions
Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years)
Short bowel syndrome
Previous treatments with natalizumab, efalizumab or rituximab.
Prior extensive colonic resection, obstructive (symptomatic) intestinal stricture, abdominal abscess, active or latent tuberculosis,
Documented Clostridium difficile superinfection;
Indeterminate colitis
Concomitant leukocyte apheresis.
Any contraindication to vedolizumab therapy
Patients who denied the protocol, not ability to accept or sign consent of the protocol
Subject involved in another interventional clinical trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier Roblin, MD
Organizational Affiliation
CHU SAINT ETIENNE
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Kremlin Bicetre
City
Paris
State/Province
Le Kremlin-Bicêtre
ZIP/Postal Code
94270
Country
France
Facility Name
CHU d'Amiens
City
Amiens
ZIP/Postal Code
80000
Country
France
Facility Name
CHU L'Archet
City
Nice
ZIP/Postal Code
06200
Country
France
Facility Name
CHU Lyon-Sud, Hospices Civils de Lyon, PIERRE-BENITE
City
Pierre Bénite
ZIP/Postal Code
69230
Country
France
Facility Name
Chu Saint Etienne
City
Saint Etienne
ZIP/Postal Code
42055
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Value of Pharmacokinetic Assays in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease
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