Management of Moderate POstoperative Recurrence in Crohn's Disease: a randoMizEd contROLled Trial of Therapeutic Escalation, the POMEROL Trial. (POMEROL)

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Status and phase: Enrolling; Phase 4

Conditions: Crohn Disease

Treatments: Drug: Immunosuppressors (Thiopurines or Methotrexate); Drug: Infliximab CT-P13

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05072782

GT-2021-01

Details and patient eligibility

About

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.

Full 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

Enrollment: 360 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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360 participants in 2 patient groups

Status quo arm

Other group

Description:

If the patient received no prophylactic therapy after resection, no treatments will be started. If the patient received a prophylactic therapy after resection, the same will be continued at the same dose.

Treatment:

Drug: Immunosuppressors (Thiopurines or Methotrexate)

Therapy escalation arm

Experimental group

Description:

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.

Treatment:

Drug: Infliximab CT-P13