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

Crohn Disease Clinical Trial

— POMEROL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05072782
• Other study ID #: GT-2021-01
• Status: Recruiting
• Phase: Phase 4
• Start date: December 21, 2021
• Est. completion date: June 15, 2024

Study information

• Verified date: May 2022
• Source: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Contact: Pauline riviere
• Phone: 0972576160
• Email: projet[@]getaid.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: June 15, 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Recurrence

Intervention

Drug:
• Infliximab CT-P13
Stratification 1: Infliximab-CT-P13 Stratification 2: Infliximab-CT-P13 in combination with immunosuppressors
• Immunosuppressors (Thiopurines or Methotrexate)
Stratification 1 : No treatments Stratification 2 : Immunosuppressors at same dose

Locations

Country	Name	City	State
France	GETAID	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives	Celltrion

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to clinical postoperative recurrence will be assessed	Time to clinical postoperative recurrence will be assessed	Baseline, Month 4, Month 8, Month 12
Secondary	Serious adverse events	Occurence of Serious Adverse Events	Screening, Baseline, Month 4, Month 8, Month 12
Secondary	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
Secondary	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