Fecal microbiota transplantation in Crohn’s disease as relay after anti-TNF withdrawal (MIRACLE)

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

22 Sep 2021 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Helmsley Charitable Trust

External identifiers

EU CT number

2024-511822-30-00

EudraCT number

2019-003816-29

ClinicalTrials.gov

NCT04997733

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the clinical efficacy at week 52 (V8) of FMT versus sham transplantation as a maintenance treatment following anti-TNF agent withdrawal in patients with Crohn’s disease in steroid-free clinical remission for at least 6 months under anti-TNF agent.

Secondary objectives 6

1. Compare between FMT and sham transplantation groups : relapse free survival between week 0 (V2) and 52 (V8)
2. Compare between FMT and sham transplantation groups : mucosal healing at week 52 (V8)
3. Compare between FMT and sham transplantation groups : clinical and endoscopic remission at week 52 (V8).
4. Compare between FMT and sham transplantation groups : changes in inflammation at week 6 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7) and 52 (V8). Measures of inflammation: blood cell count, CRP level, fecal calprotectin
5. Compare between FMT and sham transplantation groups : changes in Intestinal microbiota composition at week 6 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7) and 52 (V8)
6. Objective of any future ancillary study a. Identify potential microorganisms in healthy volunteers donor’s microbiota associated with positive and negative outcome. (Ancillary objective) b. Identify blood biomarkers and metabolites associated with maintenance of clinical remission.

Conditions and MedDRA coding

Crohn’s disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years and < 75 years
2. Crohn’s disease (according to the Lennard-Jones criteria) for at least 6 months
3. Patient in steroid-free clinical remission for at least 6 months under anti-TNF agent (no clinical evidence of flare nor change in Crohn’s disease specific treatment (anti-TNF, immunosuppressive, …) within 6 months before inclusion) and CDAI <150 the week before inclusion) and willing to withdraw anti-TNF treatment
4. Female of child-bearing age with an active contraception and this during at least the period of treatment
5. Patient with health insurance
6. Informed Written consent
7. Healthy volunteers donors :Regular bowel movement defined as at least 1 stool every other day and maximum 2 stools per day

Exclusion criteria 7

1. Crohn’s Disease complication requiring surgical treatment
2. Contraindication to colonoscopy or anesthesia
3. Pregnancy or breastfeeding during the study
4. Diagnosis of Crohn’s disease restricted to the upper gastrointestinal tract (oesophagus, stomac, duodenum, jejunum)
5. Patient with active perineal disease (defined as evidence of perineal abscess or active draining fistula or presence of seton or presence of perineal ulceration)
6. History of more than one small bowel resection or small intestine resection > 1 meter
7. Current stoma (Ileostomy or a colostomy) or stoma in the last 6 months or any other intra-abdominal surgery within 3 months prior to inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical remission (defined by a CDAI <150) at week 52 (V8) without any flare between week 0 (colonoscopy (V2)) and week 52 (V8). Flare is defined by a CDAI (Addendum 2) above 250 or between 150 points and 250 points with a 70-point increase from baseline (v0 : inclusion) over 2 consecutive weeks and the need to start any new treatment for CD.

Secondary endpoints 5

1. Relapse free survival rate from week 0 (V2) to week 52 (V8)
2. Proportion of endoscopic remission (SES-CD ≤2) at week 52 (V8) and change (in %) in endoscopic score (SES-CD) between week 0 (V2) and 52 (V8)
3. Clinical remission defined by a CDAI < 150 at week 52; endoscopic remission defined by a SES-CD ≤ 2.
4. Measures of inflammation: blood cell count, CRP level, fecal calprotectin at week 6 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7) and 52 (V8)
5. Microbiota composition and diversity using 16s sequencing technology at week 6 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7) and 52 (V8)

Investigational products

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

Test 2

Placebo 2

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 · 16 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 12 files

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

Application history

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