EFFICACI : EFFicacy of Intravenous Infliximab Versus Vedolizumab After Failure of subCutaneous Anti-TNF in Patients With UlCerative Colitis (EFFICACI)

November 20, 2023 updated by: Rennes University Hospital

EFFICACI : EFFicacy of Intravenous Infliximab Versus Vedolizumab After Failure of subCutaneous Anti-TNF in Patients With UlCerative Colitis : A Double Blinded Randomized Clinical Trial

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that results from immune dysregulation. Arguably, the development of Tumor Necrosis Factor (TNF) antagonists (including infliximab, adalimumab and golimumab) revolutionized the management of immune-mediated chronic diseases in the past two decades.

However, about one third of patients will not respond to a first anti-TNF treatment and 10% to 30% will loose response to anti-TNF during the follow-up.

Historically, a switch between anti-TNF was performed to recapture remission and response to anti-TNF. Recently, a new biologic therapy blocking another target has been approved and is now reimbursed during ulcerative colitis, namely vedolizumab. Vedolizumab is an anti-integrin agent avoiding the recruitment of lymphocytes specifically in inflamed gut tissue.

Emerging data suggest that a switch of therapeutic class (meaning a change of biologic target with Non-TNF-targeted biologic) in case of clinical failure or insufficient response to anti-TNF may be the best choice. This idea of a switch out of the anti-TNF class is also supported by data on drug monitoring that may help physician decision making in case of loss of response. However, no trial is currently available and ongoing to assess the best therapeutic strategy. The aim of the proposed study is to assess the best biological based strategy in patient losing response to a first subcutaneous anti-TNF (golimumab and/or adalimumab).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Design :

A prospective, multicenter, randomized, double blind clinical trial

Primary objective :

To determine whether a non-TNF-targeted biologic (vedolizumab) is superior to infliximab to treat patient with UC losing response or with a primary failure to a first subcutaneous anti-TNF drug at week 14.

Secondary objective :

  • To assess the rate of clinical response and remission at Week 54 in each group of treatments and the time to clinical response and remission from baseline ;
  • To assess the changes in faecal calprotectin levels from baseline to week 14 and 54 according to treatment ;
  • To assess the rate of colectomy and hospitalization in each treatment group ;
  • To assess the rate of mucosal healing at week 14 and 54 in each group of treatments ;
  • To assess the rate of loss of response in each group of treatments for patients responder after induction phase ;
  • To assess the changes of quality of life indexes and the disability index from baseline to week 14 and 54 ;
  • To determine the safety profile of each group of treatments ;
  • To characterize the response in each group of treatments according to drug monitoring of the first anti-TNF agent ;
  • To describe the pharmacokinetics of infliximab and vedolizumab as second-line treatment of UC and explore the sources of pharmacokinetic inter-individual variability ;
  • To identify predictive factors of response to the treatment, including pharmacokinetic features

Expected findings and impact:

The patients include in the clinical will not lose any benefit since both treatments are actually indicated and effective in this condition. In both arm of treatment, patients will receive an effective treatment.

The study will optimize physician decision making to decrease the disease activity period in UC patients with known consequence such as hospitalisation, surgery, work cessations with related cost effects.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80054
        • Recruiting
        • Centre Hospitalier Universitaire d'Amiens-Picardie
        • Contact:
        • Principal Investigator:
          • Mathurin FUMERY, MD
      • Besançon, France, 25030
        • Recruiting
        • Centre Hospitalier Universitaire de Besancon
        • Contact:
          • Lucine Vuitton, MD
        • Contact:
        • Principal Investigator:
          • Lucine VUITTON, MD
      • Bordeaux, France, 33600
        • Recruiting
        • Centre hospitalier Universitaire de Bordeaux
        • Contact:
          • David Laharie, MD
        • Contact:
        • Principal Investigator:
          • David LAHARIE, MD
      • Caen, France, 14033
        • Recruiting
        • Centre Hospitalier Universitaire de Caen
        • Contact:
          • Clea Rouillon, MD
        • Contact:
        • Principal Investigator:
          • Cléa ROUILLON, MD
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • Centre Hospitalier Universitaire de Clermont-Ferrand
        • Contact:
          • Anthony Buisson, MD
        • Contact:
        • Principal Investigator:
          • Anthony BUISSON, MD
      • Clichy, France, 92110
        • Recruiting
        • Assistance Publique des Hôpitaux de Paris - Hôpital Beaujon
        • Contact:
          • Lore BILLIAUWS, MD
        • Contact:
        • Principal Investigator:
          • Lore BILLIAUWS, MD
      • Créteil, France, 94000
        • Recruiting
        • Assistance Publique des Hôpitaux de Paris - Hôpital Henri Mondor
        • Contact:
          • Mathieu Uzzan, MD
        • Contact:
        • Principal Investigator:
          • Mathieu UZZAN, MD
      • Lille, France, 59037
        • Recruiting
        • Centre Hospitalier Universitaire de Lille
        • Contact:
          • Maria Nachury, MD
        • Contact:
        • Principal Investigator:
          • Maria NACHURY, MD
      • Lorient, France, 56000
        • Withdrawn
        • Centre Hospitalier de Bretagne Sud
      • Lyon, France, 69495
        • Recruiting
        • Hospices Civils de LYON
        • Contact:
          • Stephane Nancey, MD
        • Contact:
        • Principal Investigator:
          • Stéphane NANCEY, MD
      • Marseille, France
        • Recruiting
        • Assistance Publique des Hôpitaux de Marseille
        • Contact:
          • Mélanie SERRERO, MD
        • Principal Investigator:
          • Mélanie SERRERO, MD
      • Montpellier, France, 34090
        • Recruiting
        • Centre Hospitalier Universitaire de Montpellier
        • Contact:
          • Romain Altwegg, MD
        • Contact:
        • Principal Investigator:
          • Romain Altwegg, MD
      • Nancy, France, 54500
        • Recruiting
        • Centre Hospitalier Universitaire de Nancy
        • Contact:
          • Laurent PEYRIN-BIROULET, MD
        • Contact:
        • Principal Investigator:
          • Laurent PEYRIN-BIROULET, MD
      • Nantes, France, 44093
        • Recruiting
        • Centre Hospitalier Universitaire de Nantes
        • Contact:
          • Arnaud BOURREILLE, MD
        • Contact:
        • Principal Investigator:
          • Arnaud BOURREILLE, MD
      • Nice, France, 06202
        • Recruiting
        • Centre Hospitalier Universitaire de Nice
        • Contact:
          • Xavier Hebuterne, MD
        • Contact:
        • Principal Investigator:
          • Xavier HEBUTERNE, MD
      • Nîmes, France
        • Recruiting
        • Centre Hospitalier Universitaire de Nîmes
        • Contact:
          • Ludovic CAILLO, MD
        • Principal Investigator:
          • Ludovic CAILLO, MD
      • Paris, France, 75010
        • Recruiting
        • Assistance Publique des Hôpitaux de Paris - Hôpital Saint-Louis
        • Contact:
          • Matthieu Allez, MD
        • Contact:
        • Principal Investigator:
          • Matthieu ALLEZ, MD
      • Saint-Brieuc, France, 22000
        • Recruiting
        • Centre Hospitalier de Saint-Brieuc
        • Contact:
          • Jean-Bernard DELOBEL, MD
        • Contact:
        • Principal Investigator:
          • Jean-Bernard DELOBEL, MD
      • Saint-Malo, France, 35400
        • Withdrawn
        • Centre Hospitalier de Saint-Malo
      • Saint-Étienne, France, 42055
        • Recruiting
        • Centre Hospitalier Universitaire de Saint-Etienne
        • Contact:
          • Xavier Roblin, MD
        • Contact:
        • Principal Investigator:
          • Xavier Roblin, MD
      • Strasbourg, France, 67098
        • Withdrawn
        • Centre Hospitalier Universitaire de Strasbourg
      • Toulouse, France
        • Recruiting
        • Centre Hospitalier Universitaire de Toulouse
        • Contact:
          • Cyrielle GILLETTA de SAINT-JOSEPH, MD
        • Principal Investigator:
          • Cyrielle GILLETTA de SAINT-JOSEPH, MD
    • Bretagne
      • Vannes, Bretagne, France, 56017
        • Withdrawn
        • Centre Hospitalier Bretagne Atlantique

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or non-pregnant female, non-lactating female;
  • 18 years of age or older and less than 75 years ;
  • Documented diagnosis of UC for at least 6 months ;
  • Left side colitis or pancolitis ;
  • Moderate to severe disease according to a Mayo score equal or above 6 with a Mayo endoscopic sub-score of 2 or 3 ;
  • Active disease despite ongoing treatment with adalimumab or golimumab for at least 12 weeks (inadequate response, failure, loss of response or intolerance) ;
  • Ability of the subject to participate fully in all aspects of this clinical trial ;
  • Written informed consent must be obtained and documented ;
  • Naïve to Janus kinase inhibitor (JAK inhibitor) ;
  • Affiliation to the national health insurance.

Non inclusion Criteria:

  • Contraindication to continue TNF antagonist (ongoing abscess(es), clinical suspicion of tuberculosis, past allergic reaction) ;
  • Contraindication to vedolizumab treatment ;
  • Steroid treatment > 20 mg/day for at least two weeks before baseline ;
  • Proctitis ;
  • Stoma ;
  • Proctocolectomy or subtotal colectomy ;
  • Planned surgery within the year of the trial ;
  • Previous exposure to vedolizumab or infliximab ;
  • History of cancer during the past 5 years ;
  • Pregnancy or breastfeeding
  • Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.
  • Ongoing participation to another interventional study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Infliximab
Infliximab : The treatment is infused at a dose of 5 mg/kg at week 0, 2 and 6 and then every 8 weeks.
Drug: Infliximab
Infliximab : The treatment is infused at a dose of 5 mg/kg at week 0, 2 and 6 and then every 8 weeks.
Other Names:
  • Infliximab injection
Experimental: Vedolizumab
Vedolizumab : The treatment is infused at a dose of 300 mg at week 0, 2 and 6 and then every 8 weeks.
Drug: Vedolizumab Injection
Vedolizumab : The treatment is infused at a dose of 300 mg at week 0, 2 and 6 and then every 8 weeks.
Other Names:
  • Vedolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission
Time Frame: Week 14
The rate of patients with clinical and endoscopic steroid free-remission (Mayo score ≤ 2 without subscore > 1) at week 14
Week 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mayo score
Time Frame: Week 54
Mayo score at week 54
Week 54
Faecal calprotectin level
Time Frame: At week 14 and 54
Faecal calprotectin level at week 14 and 54
At week 14 and 54
Colectomy or hospitalization for disease flare
Time Frame: through study completion, an average of 1 year
Colectomy or hospitalization for disease flare during the study period
through study completion, an average of 1 year
Endoscopic subscore of the mayo Score
Time Frame: at week 14 and 54
Endoscopic subscore of the mayo Score at week 14 and 54 Partial Mayo score at week 2, 6, 14, 54. Endoscopic subscore of the Mayo score : from 0 (better score) to 3 (worse score)
at week 14 and 54
Partial Mayo score
Time Frame: at week 2, 6, 14, 54
Partial Mayo score at week 2, 6, 14, 54. Partial Mayo score : from 0 (better score) to 9 (worse score)
at week 2, 6, 14, 54
Inflammatory Bowel Disease Questionnaire (IBDQ) index
Time Frame: at baseline week 14 and 54
IBDQ index at baseline week 14 and 54
at baseline week 14 and 54
Inflammatory Bowel Disease-Disk (IBD-Disk)
Time Frame: at baseline week 14 and 54
IBD-Disk at baseline week 14 and 54
at baseline week 14 and 54
Inflammatory Bowel Disease-Disability Index (IBD-DI)
Time Frame: at baseline week 14 and 54
IBD-DI at baseline week 14 and 54
at baseline week 14 and 54
Adverse events
Time Frame: through study completion, an average of 1 year
Rate and type of adverse events during the study period
through study completion, an average of 1 year
Last trough concentration of the first subcutaneous agent
Time Frame: baseline
Last trough concentration of the first subcutaneous agent at the time of the loss of response
baseline
anti-drug antibodies concentration
Time Frame: baseline
anti-drug antibodies concentration at the time of the loss of response and
baseline
Blood trough concentration of infliximab or vedolizumab
Time Frame: at baseline, weeks 0, 2, 6, 14 and 54
Trough concentration of infliximab or vedolizumab at each visit and anti-drug antibodies concentration (blood concentration)
at baseline, weeks 0, 2, 6, 14 and 54
Fecal trough concentration of infliximab or vedolizumab
Time Frame: at baseline, weeks 0, 2, 6, 14 and 54
Trough concentration of infliximab or vedolizumab at each visit and anti-drug antibodies concentration (fecal concentration)
at baseline, weeks 0, 2, 6, 14 and 54

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rennes University Hospital

Investigators

  • Principal Investigator: Guillaume BOUGUEN, MD, Rennes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 4, 2019

Primary Completion (Estimated)

January 4, 2024

Study Completion (Estimated)

January 4, 2025

Study Registration Dates

First Submitted

September 18, 2018

First Submitted That Met QC Criteria

September 19, 2018

First Posted (Actual)

September 20, 2018

Study Record Updates

Last Update Posted (Estimated)

November 21, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 35RC17_8841_EFFICACI
  • 2018-002673-21 (EudraCT Number)
  • 2018-66-PP (Other Identifier: CPP Sud-Est I)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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