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Value of Pharmacokinetic Assays in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease (VEDO-PREDIRESP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02768532
Recruitment Status : Recruiting
First Posted : May 11, 2016
Last Update Posted : July 26, 2019
Sponsor:
Collaborators:
Theradiag
Takeda
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

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.


Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Vedolizumab Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 93 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 1, 2016
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Vedolizumab

Arm Intervention/treatment
Experimental: Crohn's disease patients
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.
Drug: Vedolizumab

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.

Other Name: Entyvio




Primary Outcome Measures :
  1. Vedolizumab concentration at week 6 [ Time Frame: 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 :
  1. Vedolizumab concentration at week 14 [ Time Frame: 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.

  2. Concentration of Vedolizumab at week 2 [ Time Frame: Week 2 ]
    Investigating whether the Vedolizumab concentrations measured at week 2 are predictive of a clinical response and clinical remission at week 10.

  3. Presence of specific antibodies (anti-integrins) at week 2 [ Time Frame: 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.

  4. Concentration of Vedolizumab at week 14 [ Time Frame: Week 14 ]
    Investigating whether the Vedolizumab concentrations measured at week 14 are predictive of a clinical response and clinical remission at week 54.

  5. Presence of specific antibodies (anti-integrins) at week 14 [ Time Frame: 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.

  6. Vedolizumab and calprotectin levels at week 2 [ Time Frame: 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.

  7. Vedolizumab and calprotectin levels at week 14 [ Time Frame: 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.

  8. Intra and inter-individual heterogeneity of Vedolizumab levels [ Time Frame: Week 54 ]
    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.

  9. Proportion of loss of clinical response [ Time Frame: Week 54 ]
    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.

  10. Vedolizumab serum levels [ Time Frame: Week 54 ]
    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.

  11. Concentration of Vedolizumab at week 54 [ Time Frame: Week 54 ]
    Comparing the level of Vedolizumab between patients achieving a clinical remission or not at week 54.

  12. Specific antibodies (anti-integrins) level at week 54 [ Time Frame: Week 54 ]
    Comparing the specific antibodies (anti-integrins) levels between patients achieving a clinical remission or not at week 54.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • Previous treatment with adalimumab within 30 days prior enrollment or infliximab and certolizumab pegol within 60 days before enrollment. This deadline can be shortened by judgment of investigator.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02768532


Contacts
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Contact: Xavier Roblin, MD xavier.roblin@chu-st-etienne.fr
Contact: Florence Rancon, CRA florence.rancon@chu-st-etienne.fr

Locations
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France
CHU Kremlin Bicetre Not yet recruiting
Paris, Le Kremlin-Bicêtre, France, 94270
Contact: Franck CARBONNEL, MD       fcarbonnel7@gmail.com   
Principal Investigator: Franck Carbonnel, MD         
CHU d'Amiens Not yet recruiting
Amiens, France, 80000
Contact: Jean-Louis Dupas, MD       dupas.jean-louis@chu-amiens.fr   
Principal Investigator: Jean-Louis Dupas, MD         
CHU L'Archet Not yet recruiting
Nice, France, 06200
Contact: Jérôme Filippi       filippi.j@chu-nice.fr   
Principal Investigator: Jérôme Filippi, MD         
CHU Lyon-Sud, Hospices Civils de Lyon, PIERRE-BENITE Recruiting
Pierre Bénite, France, 69230
Contact: Stephane Nancey, MD       stephane.nancey@chu-lyon.fr   
Principal Investigator: Stephane Nancey, MD         
Sub-Investigator: Gilles Boschetti, MD         
Chu Saint Etienne Recruiting
Saint Etienne, France, 42055
Contact: Xavier Roblin, MD       xavier.roblin@chu-st-etienne.fr   
Principal Investigator: Xavier Roblin, MD         
Sub-Investigator: Nicolas Willet, MD         
Sub-Investigator: Emilie Del Tedesco, MD         
Sub-Investigator: Pauline Veyrard, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Theradiag
Takeda
Investigators
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Principal Investigator: Xavier Roblin, MD CHU SAINT ETIENNE

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Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT02768532    
Other Study ID Numbers: 1608051
2016-001587-11 ( EudraCT Number )
First Posted: May 11, 2016    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Crohn's disease
Vedolizumab
TNF (Tumor Necrosis Factor)
Clinical response
Clinical remission
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vedolizumab
Gastrointestinal Agents