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

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.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Immunosuppressors (Thiopurines or Methotrexate); Drug: Infliximab CT-P13

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

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Pauline riviere; Phone Number: 0972576160; Email: projet@getaid.org
• Study Contact Backup: Name: Marie COISNON; Phone Number: 0972576160; Email: mcoisnon@getaid.org

Study Locations

• France
  • Paris, France, 75009
    • Recruiting
    • getaid
    • Contact: Marie COISNON; Email: mcoisnon@getaid.org
    • Contact: Charlotte Mailhat; Email: projet@getaid.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Status quo arm; 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.	Drug: Immunosuppressors (Thiopurines or Methotrexate); Stratification 1 : No treatments Stratification 2 : Immunosuppressors at same dose
Experimental: 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.	Drug: Infliximab CT-P13; Stratification 1: Infliximab-CT-P13 Stratification 2: Infliximab-CT-P13 in combination with immunosuppressors; Other Names: Remsima

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with an i0-i1 modified Rutgeerts score at 12 months.	Number of patients with an i0-i1 modified Rutgeerts score at 12 months.	Month12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with an i3-i4 modified Rutgeerts score at 12 months	Number of patients with an i3-i4 modified Rutgeerts score at 12 months	Month 12
Proportion of patients with an i2b-i3-i4 modified Rutgeerts score at 12 months	Proportion of patients with an i2b-i3-i4 modified Rutgeerts score at 12 months	Month 12
Proportion of patients with an i0 modified Rutgeerts score at 12 months	Proportion of patients with an i0 modified Rutgeerts score at 12 months	Month 12
Patient Reporting Outcome score at 12 months.	Patient Reporting Outcome score at 12 months will be assessed for the evaluation of disease activity (clinical remission).	Screening, Baseline, week 2, week 6, Month 4, Month 8, Month 12
Clinical postoperative recurrence	Clinical postoperative recurrence within 12 months defined by : 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 Average daily Stool frequency, average daily Abdominal Pain score, CRP and Calprotectin feacal will be combined to report the clinical postoperative recurrence (this outcome is is expressed without units)	Baseline, Month 4, Month 8, Month 12
Surgical recurrence within 12 months	Surgical recurrence within 12 months defined by need for a new ileocolonic resection. Proportion of surgical recurrence within 12 months	Baseline, Month 4, Month 8, Month 12
Endoscopic dilatation within 12 months	Endoscopic dilatation within 12 months defined by a 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 Proportion of endoscopic dilatation within 12 months	Baseline, Month 4, Month 8, Month 12
Time to clinical postoperative recurrence will be assessed	Time to clinical postoperative recurrence will be assessed	Baseline, Month 4, Month 8, Month 12
Serious adverse events	Occurence of Serious Adverse Events	Screening, Baseline, Month 4, Month 8, Month 12
Quality of life: EQ5D-5L questionnaires	Quality of life will be assessed with the EQ5D-5L questionnaire	Baseline, week 2, week 6, Month 4, Month 8, Month 12
Work productivity and activity impairement questionnaires	Work productivity and activity impairement will be assessed with work productivity and activity impairement questionnaires	Baseline, week 2, week 6, Month 4, Month 8, Month 12

Collaborators and Investigators

• Sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Collaborators: Celltrion

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 15, 2024

Study Registration Dates

• First Submitted: August 18, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Crohn's Disease; Rutgeerts score i2; Infliximab CT-P13; Postoperative reccurrence; Ileocolonic resection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Recurrence; Crohn Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Infliximab
• Other Study ID Numbers: GT-2021-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No