Crohn's disease patients having an i2 endoscopic postoperative recurrence 6-12 months after ileocolonic anastomosis.
Conditions
Interventions
Trade Name: Remsima 100 mg powder for solution for infusion
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg/kg mill
Sponsors
GETAID
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age > 18 years - Diagnosis of Crohn's disease according to usual criteria - Intestinal resection with ileocolonic anastomosis removing all Crohn’s disease inflammatory lesions performed within the last 6-12 months (patients who underwent a two stage surgical procedure are also eligible if the endoscopic evaluation is performed 6-12 months after restoration of the fecal stream) - Postoperative endoscopy performed between 6 and 12 months +/- 2 months after ileocolonic anastomosis reaching the neoterminal ileum - Postoperative endoscopic recurrence classified i2 according to the Rutgeerts score at 6-12 months, validated by a blinded central reading - The patient is willing to start infliximab CT-P13 at a fixed schedule of 2 intravenous infusions at week 0 and week 2 followed by subcutaneous CT-P13 every other week from week 6 onwards Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Patients with an ostomy - Patients with ulcerative colitis or IBD type unclassified - Patients with an ileorectal or ileal pouch-anal anastomosis - Patients exposed to infliximab before index surgery with a primary non-response (no clinical effect after 2 infusions or at the discretion of the treating gastroenterologist) or history of infusion reactions to infliximab or history of detectable anti-infliximab antibodies - Patients with symptoms of active CD, defined as average daily SF = 3.5 and average daily AP score = 1.5, having started after a free interval without symptoms of one month after surgery - Patients with obstructive symptoms of CD defined by a CDOS > 4 (15) (see Appendix for description of the score). Asymptomatic patients receiving an endoscopic dilatation for a non-passable stenosis at baseline endoscopy in centres where it is a current practice to estimate the lesions extent can be included. - Patients treated with any biological therapy (except for intraocular injections) or an investigational medical product after index surgery - Patients having started thiopurines or methotrexate more than 6 weeks after ileocolonic anastomosis with restoration of the faecal stream - Patients in whom not all inflammatory lesions have been removed at index surgery: e.g. incomplete ileo-colonic resections, active colitis. - Patients with active perianal Crohn's disease - Patients with a contraindication to infliximab: cancer in the 5 years prior to inclusion, excluding non-melanoma skin cancer, active tuberculosis or untreated latent tuberculosis, moderate or severe heart failure, HIV or HBV infection (serology < 3 months), recent live vaccination (within 4 weeks of baseline). - Pregnant women - Patients under legal protection or unable to express their consent. - Patients not affiliated to a health insurance system. - Patients deprived of liberty by judiciary or administrative decision or hospitalized without consent or admitted in a sanitary or social institution for another reason than research.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the proportion of CD patients without endoscopic postoperative recurrence (i0-i1) at 12 months (M12) in the arm receiving therapy escalation compared to status quo arm in patients having an i2 endoscopic postoperative recurrence 6-12 months after ileocolonic anastomosis.;Secondary Objective: - To compare the proportions of patients with severe endoscopic recurrence (i3-i4) between both arms and the proportion of i2b-i3-i4 patients at 12 months (M12) between both arms - To compare the proportions of patients with clinical postoperative recurrence, surgical recurrence, need for endoscopic dilatation at 12 months (M12) between both arms. - To compare the mean change in Two Item Patient Reported Outcome (PRO2) from baseline to 12 months (M12) between both arms. - Evaluate the safety of therapy during the 12 months study period. - Evaluate the quality of life and work productivity impact during the 12 months study period. - To compare the clinical, endoscopic and surgical outcomes of 3 pre-specified subgroups: according to i2 subtype (i2a versus i2b patients), smoking status and immunosuppressant status. ;Primary end point(s): The primary endpoint will be the proportion of patients with a treatment success defined as an i0-i1 modified Rutgeerts score (mRS) at 12 months (M12) Treatment failure will be defined as: - Modified Rutgeerts score > i1 at 12 months (M12) - OR Clinical postoperative recurrence: Average daily stool frequency = 3.5 and average daily abdominal pain score = 1.5, AND * increased CRP compared to inclusion, at least + 10 mg/l * OR increased fecal calprotectin compared to inclusion, at least + 250 µg/g - OR Endoscopic dilatation defined as a need for a balloon insufflation at the ileocolonic anastomosis during an ileocolonoscopy when a non-passable stenosis was present in a patient having obstructive symptoms (Crohn Disease Obstructive Scale - CDOS > 4) before endoscopy. Endoscopic dilatation performed in asymptomatic pa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of patients with an i3-i4 mRS at 12 months (M12) - Proportion of patients with an i2b-i3-i4 mRS at 12 months (M12) - Proportion of patients with an i0 mRS at 12 months (M12) - Two item Patient Reported Outcome (PRO2) at 12 months (13) (M12) - Clinical postoperative recurrence within 12 months after randomization : average daily stool frequency = 3.5 AND average daily abdominal pain score = 1.5 (14), AND increased CRP compared to inclusion, at least + 10 mg/l OR increased fecal calprotectin compared to inclusion, at least + 250 µg/g - Surgical recurrence within 12 months: need for a new ileocolonic resection - Endoscopic dilatation within 12 months: need for a balloon insufflation at the ileocolonic anastomosis during an ileocolonoscopy when a non-passable stenosis was present in patient with obstructive symptoms (Crohn's disease obstructive score>4 (15)) before endoscopy - Time to clinical postoperative recurrence - Serious adverse events - Quality of life: EQ5D-5L - Work productivity: Work Productivity and Activity Impairment questionnaire ;Timepoint(s) of evaluation of this end point: at M4, M8 and M12 | — |
Countries
Belgium, France, Spain
Contacts
Public ContactMarie COISNON
GETAID
Outcome results
None listed