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

NCT ID: NCT03679546

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-04
• Study Completion Date: 2025-06-16

Brief Summary

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).

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Infliximab

Infliximab : The treatment is infused at a dose of 5 mg/kg at week 0, 2 and 6 and then every 8 weeks.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

Infliximab : The treatment is infused at a dose of 5 mg/kg at week 0, 2 and 6 and then every 8 weeks.

Vedolizumab

Vedolizumab : The treatment is infused at a dose of 300 mg at week 0, 2 and 6 and then every 8 weeks.

Group Type: EXPERIMENTAL

Vedolizumab Injection

Intervention Type: DRUG

Vedolizumab : The treatment is infused at a dose of 300 mg at week 0, 2 and 6 and then every 8 weeks.

Interventions

Infliximab

Infliximab : The treatment is infused at a dose of 5 mg/kg at week 0, 2 and 6 and then every 8 weeks.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Infliximab injection; Vedolizumab

Eligibility Criteria

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.

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume BOUGUEN, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Locations

Centre Hospitalier Universitaire d'Amiens-Picardie

Amiens, , France

Centre Hospitalier Universitaire de Besançon

Besançon, , France

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, , France

Centre Hospitalier Universitaire de Caen

Caen, , France

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, , France

Assistance Publique des Hôpitaux de Paris - Hôpital Beaujon

Clichy, , France

Assistance Publique des Hôpitaux de Paris - Hôpital Henri Mondor

Créteil, , France

Centre Hospitalier Universitaire de Lille

Lille, , France

Hospices Civils de Lyon

Lyon, , France

Assistance Publique des Hôpitaux de Marseille

Marseille, , France

Centre Hospitalier Universitaire de Montpellier

Montpellier, , France

Centre Hospitalier Universitaire de Nancy

Nancy, , France

Centre Hospitalier Universitaire de Nantes

Nantes, , France

Centre Hospitalier Universitaire de Nice

Nice, , France

Centre Hospitalier Universitaire de Nîmes

Nîmes, , France

Assistance Publique des Hôpitaux de Paris - Hôpital Saint-Louis

Paris, , France

Centre Hospitalier de Saint-Brieuc

Saint-Brieuc, , France

Centre Hospitalier Universitaire de Saint-Etienne

Saint-Etienne, , France

Centre Hospitalier Universitaire de Toulouse

Toulouse, , France

Countries

France

Other Identifiers

2018-002673-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2018-66-PP

Identifier Type: OTHER

Identifier Source: secondary_id

35RC17_8841_EFFICACI

Identifier Type: -

Identifier Source: org_study_id