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

NCT02768532 | Terminated Phase 4

• 2 other identifiers: 16080512016-001587-11
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

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.

Conditions

Crohn Disease

Keywords

Crohn's disease; Vedolizumab; TNF (Tumor Necrosis Factor); Clinical response; Clinical remission

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 6

Secondary Outcomes (12)

• Vedolizumab concentration at week 14

  Week 14

• Concentration of Vedolizumab at week 2

  Week 2

• Presence of specific antibodies (anti-integrins) at week 2

  Week 2

• Concentration of Vedolizumab at week 14

  Week 14

• Presence of specific antibodies (anti-integrins) at week 14

  Week 14

Study Arms (1)

Crohn's disease patients

EXPERIMENTAL

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

Interventions

Vedolizumab DRUG

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.

Also known as: Entyvio

Crohn's disease patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Informed written consent given.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Theradiag: collaborator
• Takeda: collaborator

Study Sites (5)

CHU Kremlin Bicetre

Paris, Le Kremlin-Bicêtre, 94270, France

Location

CHU d'Amiens

Amiens, 80000, France

Location

CHU L'Archet

Nice, 06200, France

Location

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

Pierre-Bénite, 69230, France

Location

Chu Saint Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Xavier Roblin, MD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 11, 2016
• Study Start: July 1, 2016
• Primary Completion: January 11, 2022
• Study Completion: January 23, 2023
• Last Updated: June 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)