Prospective multicenter randomized controlled double-blind label study of the prophylaxis of recurrent pouchitis after fecal microbiota transplant in UC with ileo-anal anastomosis.

• Register: EUCTR
• Last refreshed on: 10 October 2018
• Main ID: EUCTR2017-004967-11-FR
• Date of registration: 06/04/2018
• Prospective Registration: Yes
• Primary sponsor: CHU Nantes
• Public title: Prospective multicenter randomized controlled double-blind label study of the prophylaxis of recurrent pouchitis after fecal microbiota transplant in UC with ileo-anal anastomosis.
• Scientific title: Poca - Poca
• Date of first enrolment: 26/06/2018
• Target sample size: 42
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004967-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: Direction de la recherche
• Affiliation: CHU de Nantes

• Name: Direction de la recherche
• Affiliation: CHU de Nantes

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female = 18 years at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to conduct the study related assessments/procedure.
3. Willing and able to adhere to the study visit scheduled and other protocol requirements.
4. Subjects must have been operated with ileal pouch anal anastomosis (IPAA) with a duration of at least 6 month prior the screening visit.
5. Subject must have a diagnosis of recurrent pouchitis defined as at least 2 episodes in the last year or relapsing immediately after a reasonable response to antibiotherapy.
6. Subject must be in remission with a Pouchitis Disease Activity Index (PDAI) < 7 at the screening
7. Subject must affiliation with social security system or beneficiary from such system
8. Female of childbearing potential must have a negative pregnancy test at screening and must agree to practice effective methods of contraception
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1. Crohn disease or indeterminate colitis
2. Anastomotic stenosis
3. Subject with prior treatment by probiotic within 3 month prior to the transplantation visit
4. Subject with prior treatment by corticosteroids within 6 weeks prior to the transplantation visit
5. Subject with prior treatment by immunosuppressors within 3 month prior to the transplantation visit
6. Prior treatment with a biologic within 3 month prior the transplantation visit
7. Documented active infection of any kind in the last 6 months
8. Absolute neutrophil count (ANC) < 1.5 x 109 /L (1,500 mm3)
9. Infection with chronic HIV
10. Pregnant female or breastfeeding
11. Chronic medical or psychiatric disease that may interfere with subject’s ability to comply with study procedures
12. Administration of investigational drug within 3 months prior to planned FMT
13. Adults under guardianship, Safeguard justice or trusteeship
14. Subject with difficulty in follow-up (vacation, job transfer, geographical distance, lack of motivation).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients operated with an IPAA for Ulcerative Colitis with active recurrent pouchitis, who respond after 4 weeks of an antibiotherapy, will be randomized
MedDRA version: 20.1 Level: LLT Classification code 10000638 Term: Active ileal inflammation System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: suspension de microbiote fécal
Product Code: PRD5973697
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Rectal use

Primary Outcome(s)

Main Objective: To compare the relapse delay after fecal microbiota transplantation versus sham transplantation for recurrent pouchitis in IPAA for ulcerative colitis.

Secondary Objective: Efficacy of fecal microbiota transplantation on the relapse rate at week 24
Efficacy of fecal microbiota transplantation on the relapse rate at week 52
Instauration of alternative treatment within week 52
Safety of a fecal microbiota transplantation in case of pouchitis
Modifications of the fecal microbiota of a patient with ileal pouch for ulcerative colitis complicated of recurrent pouchitis, in remission after antibiotherapy after fecal transplant microbiota from a healthy donor at week 8
Evolution of health-related to disability

Primary end point(s): Delay between the date of transplantation and the date of the Clinical and endoscopic relapse defined by a Pouchitis Disease Activity Index (Appendix) = 7 points.
The Pouchitis Disease Activity Index (PDAI) is a 19 point index of pouchitis activity based on both clinical symptoms and endoscopic and histologic findings . Active pouchitis is defined as a PDAI = 7 and remission is defined as a PDAI < 7. Clinical response to treatment can also be quantified by reduction in the PDAI .

Timepoint(s) of evaluation of this end point: 106 weeks

Secondary Outcome(s)

Secondary end point(s): 1- Relapse at week 24 defined as a Pouchitis Disease Activity Index (PDAI) superior or equal to 7 at week 24
2- Relapse at week 52 defined as a Pouchitis Disease Activity Index (PDAI) superior or equal to 7 at week 52
3- Delay within the transplantation and the instauration of an antibiotherapy or alternative treatment (immunosuppressive and/or biotherapy and/or corticotherapy)
4- Registered of adverse events defined by Common Terminology Criteria for Adverse Events (4.3) during 104 weeks post-transplantation according to ANSM recommendation.
5- Fecal microbiota engraftment at 8 weeks defined by :
Sorensen’s index [receiver 8 weeks after FMT vs donor] > Sorensen’s index [receiver 8 weeks after FMT vs receiver before FMT]) with Sorensen’s index [receiver 8 weeks after FMT vs donor] = 0.6. To assess this endpoint, fecal microbiota composition will be analyzed for donor sample, receiver sample before FMT and 8 weeks after FMT, using 16S sequencing (Illumina Miseq technology)
6- IBD Disability Index at weeks -5, baseline, 8, 24, 52 and unscheduled visit

Timepoint(s) of evaluation of this end point: 1_24 weeks
2_ 52 weeks
3_ 106 weeks
4_ 104 weeks post-transplantation
5_ 8 weeks
6_ weeks -5, baseline, 8 weeks, 24 weeks, 52weeks and 104 weeks

Secondary ID(s)

RC17_0021

Source(s) of Monetary Support

DGOS-PHRCN