Clinical trial NCT02768532: Value of Pharmacokinetic Assays in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease
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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Crohn Disease
Keywords: Crohn's disease
Vedolizumab
TNF (Tumor Necrosis Factor)
Clinical response
Clinical remission
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Theradiag
name: Takeda
First posted: 2016-05-11
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Vedolizumab concentration at week 6
timeFrame: Week 6
Secondary outcomes:
measure: Vedolizumab concentration at week 14
timeFrame: Week 14
measure: Concentration of Vedolizumab at week 2
timeFrame: Week 2
measure: Presence of specific antibodies (anti-integrins) at week 2
timeFrame: Week 2
measure: Concentration of Vedolizumab at week 14
timeFrame: Week 14
measure: Presence of specific antibodies (anti-integrins) at week 14
timeFrame: Week 14
measure: Vedolizumab and calprotectin levels at week 2
timeFrame: Week 2
measure: Vedolizumab and calprotectin levels at week 14
timeFrame: Week 14
measure: Intra and inter-individual heterogeneity of Vedolizumab levels
timeFrame: Week 54
measure: Proportion of loss of clinical response
timeFrame: Week 54
measure: Vedolizumab serum levels
timeFrame: Week 54
measure: Concentration of Vedolizumab at week 54
timeFrame: Week 54
measure: Specific antibodies (anti-integrins) level at week 54
timeFrame: Week 54
Other outcomes:
Locations:
city: Paris
country: France
facility: CHU Kremlin Bicetre
state: Le Kremlin-Bicêtre
city: Amiens
country: France
facility: CHU d'Amiens
city: Nice
country: France
facility: CHU L'Archet
city: Pierre Bénite
country: France
facility: CHU Lyon-Sud, Hospices Civils de Lyon, PIERRE-BENITE
city: Saint Etienne
country: France
facility: Chu Saint Etienne
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Xavier Roblin, MD
role: PRINCIPAL_INVESTIGATOR
References: