Management of moderate POstoperative recurrence in Crohn's disease: a randoMizEd contROLled trial of therapeutic escalation, the POMEROL trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe D'etude Therapeutique Des Affections Inflammatoires Du Tube Digestif

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 Dec 2021 → ongoing

Decision date (initial)

2024-05-27

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

CELLTRION HEALTH CARE

External identifiers

EU CT number

2023-508242-18-00

EudraCT number

2021-002369-17

ClinicalTrials.gov

NCT05072782

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others

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 6-12 months after ileocolonic anastomosis with restoration of the faecal stream.

Secondary objectives 6

1. To compare the proportions of patients with severe endoscopic recurrence (i3-i4) at 12 months between both arms.
2. To compare the proportions of patients with clinical postoperative recurrence, surgical recurrence, need for endoscopic dilatation at 12 months between both arms.
3. To compare the mean change in PRO2 from inclusion visit to 12 months between both arms.
4. Evaluate the safety of therapy during the 12 months study period.
5. Evaluate the quality of life and work productivity impact of therapy escalation during the 12 months study period.
6. To compare the clinical, endoscopic and surgical outcomes of i2a and i2b patients

Conditions and MedDRA coding

Crohn's disease

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age: ≥ 18 years, < or = 75 years
2. Diagnosis of Crohn's disease according to usual criteria
3. 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)
4. Postoperative endoscopy performed between 6 and 12 months +/- 2 months after ileocolonic anastomosis reaching the neoterminal ileum
5. Postoperative endoscopic recurrence classified i2 according to the Rutgeerts score at 6-12 months, validated by a blinded central reading

Exclusion criteria 15

1. Patients with an ostomy
2. Patients with ulcerative colitis or IBD type unclassified
3. Patients with an ileorectal or ileal pouch-anal anastomosis
4. 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
5. 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
6. Patients with obstructive symptoms of CD defined by a CDOS > 4 (20) (see Appendix for description of the score). Asymptomatic patients receiving an endoscopic dilatation for a non-passable stenosis at screening endoscopy in centres where it is a current practice to estimate the lesions extent can be included.
7. Patients treated with any biological therapy (except for intraocular injections) or an investigational medical product after index surgery
8. Patients having started thiopurines or methotrexate more than 6 weeks after ileocolonic anastomosis with restoration of the faecal stream
9. Patients in whom not all inflammatory lesions have been removed at index surgery: e.g. incomplete ileo-colonic resections, active colitis.
10. Patients with active perianal Crohn's disease
11. 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 inclusion visit).
12. Pregnant women
13. Patients under legal protection or unable to express their consent.
14. Patients not affiliated to a health insurance system.
15. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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) (See Appendix for the description of the score).

Secondary endpoints 11

1. Proportion of patients with an i3-i4 modified Rutgeerts score at 12 months
2. Proportion of patients with an i2b-i3-i4 modified Rutgeerts score at 12 months
3. Proportion of patients with an i0 modified Rutgeerts score at 12 months
4. Two item Patient Reported Outcome (PRO2) at 12 months (18) (M12)
5. Clinical postoperative recurrence within 12 months after randomization : average daily stool frequency ≥ 3.5 AND average daily abdominal pain score ≥ 1.5 (19), AND increased CRP compared to inclusion, at least + 10 mg/l OR increased fecal calprotectin compared to inclusion, at least + 250 μg/g
6. Surgical recurrence within 12 months: need for a new ileocolonic resection
7. 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
8. Time to clinical postoperative recurrence
9. Serious adverse events
10. Quality of life: EQ5D-5L questionnaire
11. Work productivity: Work Productivity and Activity Impairment questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe D'etude Therapeutique Des Affections Inflammatoires Du Tube Digestif

Sponsor organisation

Groupe D'etude Therapeutique Des Affections Inflammatoires Du Tube Digestif

Address

50 Rue Richer

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Groupe D'etude Therapeutique Des Affections Inflammatoires Du Tube Digestif

Contact name

Dr Pauline Rivière

Public contact point

Organisation

Groupe D'etude Therapeutique Des Affections Inflammatoires Du Tube Digestif

Contact name

charlotte mailhat

Locations

3 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications