Clinical trial NCT05072782: Management of Moderate POstoperative Recurrence in Crohn's Disease: a randoMizEd contROLled Trial of Therapeutic Escalation, the POMEROL Trial. (POMEROL)
Official title: Management of Moderate POstoperative Recurrence in Crohn's Disease: a randoMizEd contROLled Trial of Therapeutic Escalation, the POMEROL Trial. (POMEROL)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Crohn Disease
Keywords: Crohn's Disease
Rutgeerts score i2
Infliximab CT-P13
Postoperative reccurrence
Ileocolonic resection
Lead sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Sponsor class: OTHER
Collaborators: name: Celltrion
First posted: 2021-10-11
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

Brief summary: Study type : A 30 months, multicentre, open-label strategic randomized controlled trial

Population : Chron's Disease (CD) patients with an i2 endoscopic postoperative recurrence in the year following ileocolonic resection (6-12months after ileocolonic resection).

Treatments :

Stratification at inclusion according to prophylactic therapy.

Patients randomized in 2 arms:

* Status quo arm: if the patient received no prophylactic therapy, no treatment will be started; if the patient received a prophylactic therapy, the same will be continued at the same dose.
* Therapy escalation arm: infliximab-CT-P13 will be started with two intravenous infusions of 5 mg per kg bodyweight at week 0 and week 2 and subcutaneous injections of 120 mg every 2 weeks from week 6 onwards.

Main objective : To evaluate the proportion of CD patients without endoscopic postoperative recurrence (i0-i1) at 12 months in the arm receiving therapy escalation compared to status quo arm in patients having an i2 endoscopic postoperative recurrence 6-12months after ileocolonic anastomosis with restoration of faecal stream.

Detailed description: Number of patients : 360 patients in approximatively 25 sites in France.

Recruitement period : The trial duration for each patients will be 12 months from radomization (18 to 24 months from screening (ie : post-operatively))

Endpoints:

Primary endpoints: Proportion of patients with an i0-i1 modified Rutgeerts score at 12 months.

Secondary endpoints:

* Proportion of patients with an i3-i4 modified Rutgeerts score at 12 months
* Proportion of patients with an i2b-i3-i4 modified Rutgeerts score at 12 months
* Proportion of patients with an i0 modified Rutgeerts score at 12 months
* PRO2 score at 12 months
* Clinical postoperative recurrence within 12 months: average daily SF ≥ 3.5 and average daily AP 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
* 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 having obstructive symptoms (CDOS \> 4) before endoscopy
* Time to clinical postoperative recurrence
* Serious adverse events
* Quality of life: EQ5D-5L questionnaire
* Work productivity: Work Productivity and Activity Impairment questionnaire

Eligibility criteria: Inclusion Criteria:

* Crohn's disease diagnosed according usual criteria
* Bowel resection with ileocolonic anastomosis performed removing all inflammatory lesions
* Postoperative endoscopy performed between 6 and 12 months after ileocolonic anastomosis reaching the neoterminal ileum (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)
* Moderate endoscopic postoperative recurrence classified i2 according to the Rutgeerts score at 6-12 months, validated by a blinded central reading

Exclusion Criteria:

* Patients with an ostomy
* Ulcerative colitis or IBD type unclassified
* Ileorectal or ileal pouch-anal anastomosis
* Symptoms defined as average daily SF ≥ 3.5 and average daily AP score ≥ 1.5 having started after a free interval without symptoms of at least one month after surgery
* Patients with obstructive symptoms of CD defined by a CDOS \> 4
* Patients exposed to infliximab before index surgery with a primary non-response (no clinical effect after 2 infusions at the discretion of the treating gastroenterologist) or history of infusion reactions to infliximab or history of detectable anti-infliximab antibodies
* Patients treated with 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 fecal stream
* Patients in whom not all inflammatory lesions have been removed at index surgery
* 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 \< 6 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.

Primary outcomes:
measure: Number of patients with an i0-i1 modified Rutgeerts score at 12 months.
timeFrame: Month12
Secondary outcomes:
measure: Number of patients with an i3-i4 modified Rutgeerts score at 12 months
timeFrame: Month 12
measure: Proportion of patients with an i2b-i3-i4 modified Rutgeerts score at 12 months
timeFrame: Month 12
measure: Proportion of patients with an i0 modified Rutgeerts score at 12 months
timeFrame: Month 12
measure: Patient Reporting Outcome score at 12 months.
timeFrame: Screening, Baseline, week 2, week 6, Month 4, Month 8, Month 12
measure: Clinical postoperative recurrence
timeFrame: Baseline, Month 4, Month 8, Month 12
measure: Surgical recurrence within 12 months
timeFrame: Baseline, Month 4, Month 8, Month 12
measure: Endoscopic dilatation within 12 months
timeFrame: Baseline, Month 4, Month 8, Month 12
measure: Time to clinical postoperative recurrence will be assessed
timeFrame: Baseline, Month 4, Month 8, Month 12
measure: Serious adverse events
timeFrame: Screening, Baseline, Month 4, Month 8, Month 12
measure: Quality of life: EQ5D-5L questionnaires
timeFrame: Baseline, week 2, week 6, Month 4, Month 8, Month 12
measure: Work productivity and activity impairement questionnaires
timeFrame: Baseline, week 2, week 6, Month 4, Month 8, Month 12
Other outcomes:
Locations:
city: Paris
country: France
facility: GETAID
Study officials:
References: