Ulcerative Colitis Clinical Trial
— EFFICACIOfficial 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
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).
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Rennes University Hospital |
France,
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 |
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