Value of Pharmacokinetic Assays in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease

Study Purpose

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.

Recruitment Criteria

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Accepts Healthy Volunteers
No

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Study Type
Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

Trial ID:
NCT02768532

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase
Phase 4

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Lead Sponsor
Centre Hospitalier Universitaire de Saint Etienne

The person who is responsible for the scientific and technical direction of the entire clinical study.

Principal Investigator
Xavier Roblin, MD
Principal Investigator Affiliation CHU SAINT ETIENNE

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Agency Class
OtherOtherIndustry
Overall Status Recruiting
Countries France

The disease, disorder, syndrome, illness, or injury that is being studied.

Conditions
Crohn Disease
Additional Details

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.#46;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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

CHU Kremlin Bicetre, Paris, Le Kremlin-Bicêtre, France

Status

Not yet recruiting

Address

CHU Kremlin Bicetre

Paris, Le Kremlin-Bicêtre, 94270

Site Contact

Franck CARBONNEL, MD

fcarbonnel7@gmail.com

CHU d'Amiens, Amiens, France

Status

Not yet recruiting

Address

CHU d'Amiens

Amiens, , 80000

Site Contact

Jean-Louis Dupas, MD

dupas.jean-louis@chu-amiens.fr

CHU L'Archet, Nice, France

Status

Not yet recruiting

Address

CHU L'Archet

Nice, , 06200

Site Contact

Jérôme Filippi

filippi.j@chu-nice.fr

Pierre Bénite, France

Status

Recruiting

Address

CHU Lyon-Sud, Hospices Civils de Lyon, PIERRE-BENITE

Pierre Bénite, , 69230

Site Contact

Stephane Nancey, MD

stephane.nancey@chu-lyon.fr

Chu Saint Etienne, Saint Etienne, France

Status

Recruiting

Address

Chu Saint Etienne

Saint Etienne, , 42055

Site Contact

Xavier Roblin, MD

xavier.roblin@chu-st-etienne.fr

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