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

Ulcerative Colitis Clinical Trial

— EFFICACI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03679546
• Other study ID #: 35RC17_8841_EFFICACI
• Secondary ID: 2018-002673-2120
• Status: Recruiting
• Phase: Phase 4
• Start date: January 4, 2019
• Est. completion date: January 4, 2025

Study information

• Verified date: November 2023
• Source: Rennes University Hospital
• Contact: Guillaume BOUGUEN, MD
• Phone: 0299284321
• Email: guillaume.bouguen[@]chu-rennes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: January 4, 2025
• Est. primary completion date: January 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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

Locations

Country	Name	City	State
France	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	Centre Hospitalier de Bretagne Sud	Lorient
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-Étienne
France	Centre Hospitalier de Saint-Malo	Saint-Malo
France	Centre Hospitalier Universitaire de Strasbourg	Strasbourg
France	Centre Hospitalier Universitaire de Toulouse	Toulouse
France	Centre Hospitalier Bretagne Atlantique	Vannes	Bretagne

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Remission	The rate of patients with clinical and endoscopic steroid free-remission (Mayo score = 2 without subscore > 1) at week 14	Week 14
Secondary	Mayo score	Mayo score at week 54	Week 54
Secondary	Faecal calprotectin level	Faecal calprotectin level at week 14 and 54	At week 14 and 54
Secondary	Colectomy or hospitalization for disease flare	Colectomy or hospitalization for disease flare during the study period	through study completion, an average of 1 year
Secondary	Endoscopic subscore of the mayo Score	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
Secondary	Partial Mayo score	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
Secondary	Inflammatory Bowel Disease Questionnaire (IBDQ) index	IBDQ index at baseline week 14 and 54	at baseline week 14 and 54
Secondary	Inflammatory Bowel Disease-Disk (IBD-Disk)	IBD-Disk at baseline week 14 and 54	at baseline week 14 and 54
Secondary	Inflammatory Bowel Disease-Disability Index (IBD-DI)	IBD-DI at baseline week 14 and 54	at baseline week 14 and 54
Secondary	Adverse events	Rate and type of adverse events during the study period	through study completion, an average of 1 year
Secondary	Last trough concentration of the first subcutaneous agent	Last trough concentration of the first subcutaneous agent at the time of the loss of response	baseline
Secondary	anti-drug antibodies concentration	anti-drug antibodies concentration at the time of the loss of response and	baseline
Secondary	Blood trough concentration of infliximab or vedolizumab	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
Secondary	Fecal trough concentration of infliximab or vedolizumab	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