REBALANCE UC : impact of Fecal Microbiota Transplantation in ulcerative colitis:a randomized, sham controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

6 Dec 2024 → ongoing

Decision date (initial)

2024-12-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health

External identifiers

EU CT number

2024-511863-27-01

EudraCT number

2017-003802-42

ClinicalTrials.gov

NCT03483246

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Compare in patient with ulcerative colitis who achieved clinical remission using systemic corticosteroids, the efficacy of fecal microbiota transplantation vs sham-transplantation on steroid-free clinical and endoscopic remission at week 12.

Secondary objectives 9

1. Comparison between FMT and sham-transplantation on the efficacy on steroid-free clinical remission at week 12
2. Comparison between FMT and sham-transplantation on steroid-free endoscopic response at week 12
3. Comparison between FMT and sham-transplantation on the efficacy on steroid-free clinical remission at week 24
4. Comparison between FMT and sham-transplantation on the efficacy on steroid-free endoscopic remission at week 12
5. Comparison between FMT and sham-transplantation on The composition of intestinal microbiota at week 12 and 24 compared to baseline and healthy volunteers donor’s microbiota
6. Comparison between FMT and sham-transplantation on the tolerance and safety
7. Comparison between FMT and sham-transplantation on inflammatory biological parameters at each visit up to week 24
8. Comparison between FMT and sham-transplantation on endoscopic lesions at colonoscopy (baseline) and sigmoidoscopy (week 12)
9. Objective of any future ancillary study : Identify potential microorganisms in healthy volunteers donor’s microbiota associated with positive and negative outcome. - Identify changes in oral microbiota in patients and in comparison with oral microbiota of healthy volunteers donors and associated with positive and negative outcome - Identify blood biomarkers and metabolites associated with positive and negative outcome

Conditions and MedDRA coding

Adult patients with ulcerative colitis diagnosed for at least 3 months

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years and < 75 years
2. Ulcerative colitis (according to the Lennard-Jones criteria) diagnosed for at least 3 months and: - Currently active (PMC score > 1) and planned to be treated by systemic corticosteroids (minimum 40mg prednisone equivalent daily) or - Currently treated by systemic corticosteroid (minimum 40mg prednisone equivalent daily) within maximum 3 weeks or "REBALANCE UC" protocol, version 12-0 of 04/07/2024 8/63 This document is the property of DRCI / APHP. All reproduction is strictly prohibited. Version date: January 2017 - Steroid dependent patients (at least one unsuccessful attempt to discontinue steroid within the last 6 months before inclusion)
3. Female of child-bearing age with an active contraception and this during at least the period of treatment until the end of active follow-up period (week 24)
4. Patient with health insurance (AME except)
5. Informed Written consent

Exclusion criteria 7

1. UC Complication requiring surgical treatment
2. Patient treated with high dose corticosteroid more than three weeks before inclusion (≥40mg prednisone equivalent daily) except in case of steroid-dependence
3. Contraindication to colonoscopy or anesthesia
4. Pregnancy or breastfeeding (see definitions in annex C of the protocol)
5. Treatment preceding the colonoscopy with: - intravenous infliximab and/or vedolizumab and/or ustekinumab (< 6 weeks before the planned date of the colonoscopy) and/or subcutaneous infliximab (<2 weeks before the planned date of the colonoscopy), and /or adalimumab (<2 weeks before the planned date of the colonoscopy) and/or golimumab and/or tofacitinib (<4 weeks before the planned date of the colonoscopy) - immunosuppressant (thiopurine, methotrexate, tacrolimus or other classical immunosuppressant) started or stopped < 3 months before the planned date of the colonoscopy - Antibiotics, antifungic or probiotics treatment < 4 weeks before the planned date of the colonoscopy
6. Participation in any other interventional study
7. Patients under legal protection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Steroid-free clinical and endoscopic remission at week 12 is defined as a total Mayo score of 2 or lower and no subscore higher than 1 and mucosal healing defined as an endoscopic subscore of 0 or 1 (sigmoidoscopy).

Secondary endpoints 8

1. Steroid-free clinical remission is defined as a Partial Mayo Clinic score of 0 or 1
2. Steroid-free endoscopic response is defined as a Mayo endoscopy subscore of 1 or less, with a reduction of at least 1 point from baseline
3. Steroid-free clinical remission is defined as a Partial Mayo Clinic score of 0 or 1
4. Steroid-free endoscopic remission is defined as Endoscopic Mayo Clinic subscore of 0.
5. Microbiota composition and diversity assessed by 16s sequencing at week 12 and 24, compared to baseline and to healthy volunteers donor’s microbiota.
6. Proportion of adverse events in each group (Abdominal pain, Nausea, vomiting, fever, modified intestinal transit, an episode of infection)
7. Inflammatory biological parameter: CRP, fecal calprotectin, platelet number
8. Endoscopic lesions at coloscopy and sigmoidoscopy (week 12) by endoscopic Mayo score and UCEIS score

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Harry SOKOL

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Harry SOKOL

Locations

1 EU/EEA country · 12 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 7 files

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

Application history

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