Fecal microbiota transplantation for primary sclerosing cholangitis - randomized study versus sham transplantation (FMT-SCLER).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2025-12-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess in patients with PSC the efficacy of FMT versus sham transplantation on ALP and bilirubin at week 48 (surrogate markers of transplantation-free survival in PSC patients) in addition to standard UDCA therapy.

Secondary objectives 10

1. Compare the efficacy of FMT on normalization of ALP and bilirubin level at week 12, 24, 36 and 48 individually
2. Compare the efficacy of FMT on biochemical liver tests at week 12, 24 36 and 48 (ALP, GGT, AST, ALT and bilirubin)
3. Compare the efficacy of FMT on liver fibrosis progression assessed by transient elastography at week 48 versus week 0.
4. Compare the PSC prognostic scores at week 0 24 and 48.
5. Compare the occurrence of liver events (decompensation of cirrhosis, acute cholangitis, jaundice, need for endoscopic retrograde cholangiopancreatography (ERCP)) during the study period
6. Compare the safety during the study period
7. Compare the symptoms, quality of life, and fatigue at week 24 and 48; pruritus at week 12, 24, 36 and 48
8. Compare the changes in bile acids, cholangiographic abnormalities between week 48 and week 0.
9. Compare the changes in IBD clinical symptoms, fecal calprotectin and endoscopic scores between week 48 and week 0.
10. Compare the changes in gut microbiota composition at week 12, 24, 36 and 48.

Conditions and MedDRA coding

Primary Sclerosing Cholangitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Males or females
2. Age ≥18 and ≤75 years
3. Large duct PSC verified by retrograde, operative, percutaneous or magnetic resonance cholangiography (MRC) demonstrating intrahepatic and /or extrahepatic biliary duct changes consistent with PSC
4. IBD diagnosed according to international guidelines (presence of endoscopic and histologic signs)
5. IBD inactive for at least 6 months (defined by no evidence of flare and no change in treatment)
6. ALP ≥ 1.3 ULN (at least 2 times within a 3 months pre-inclusion period) or elevated total bilirubin ≤50mol/l (with concomitant elevated direct bilirubin).
7. Treatment with UDCA (13-23 mg/kg/d) for at least 6 months and at the same dosage for at least 3 months
8. Using contraceptive in women of childbearing potential. Women of childbearing potential, i.e. fertile, following menarche and until becoming post-menopaused unless permanently sterile, who are sexually active have to apply a highly effective method of birth control with a low failure rate (i.e. less than 1% per year) when used constantly and correctly.
9. Written informed consent signed
10. Subject affiliated to the French Social Security System

Exclusion criteria 27

1. Small duct PSC
2. Autoimmune hepatitis defined by the presence of moderate to severe interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: AST or ALT > 5 ULN, Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN
3. Secondary sclerosing cholangitis (notably IgG4-associated cholangitis)
4. Cirrhosis defined by Liver elastometry >14.4 kPa or by current or past decompensation of cirrhosis
5. AST or ALT > 7 ULN in the last 3 months
6. Platelets count in the last 3 months < 100 000/mm3
7. Albumin in the last 3 months <35g/L
8. Prothrombin index in the last 3 months < 70%
9. Hepatic comorbidity: HBV infection (defined by positive Ag HBS), HCV infection (defined by positive HCV RNA), alcohol abuse (defined by alcohol intake > 30g/day), metabolic dysfunction associated steatohepatitis, primary biliary cholangitis, Hemochromatosis, Wilson disease, α1-antitrypsin deficiency, celiac disease
10. History of acute cholangitis in the last 3 months prior to inclusion or current acute cholangitis
11. HIV infection
12. Prior liver transplantation
13. Endoscopic treatment for bile duct stenosis ≤ 3 months prior to inclusion or planned within 3 months post randomization date
14. History of or established or suspected hepatobiliary carcinoma.
15. Any severe comorbidity that may reduce life expectancy
16. History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to inclusion)
17. Dosage changes of treatment for liver disease in the last 3 months or new treatment for liver disease started in the last 3 months
18. History of colorectal carcinoma or high-grade dypsplasia in previous screening colonoscopy
19. History of total colectomy
20. Current active IBD defined by a partial Mayo score > 2 in patients with ulcerative colitis (UC), unclassed colitis or a Crohn’s Disease Activity Index (CDAI) > 150 in patients with Crohn’s disease
21. Changes in IBD treatment or initiation of a new treatment for IBD in the last 3 months
22. Current treatment with biologics (anti-TNF agent, vedolizumab, ustekinumab) or JAK inhibitors (tofacitinnib) or prednisone > 10 mg/day or budesonide > 3 mg /day) (or treatment initiated less than one month)
23. Any contra-indication to swallow capsules
24. Renal insufficiency (clearance<60 ml/min)
25. Unable to consent, subject to legal or administrative decision (protection measure or deprivation of liberty) or involuntary psychiatric care.
26. Inclusion in another clinical trial on medicinal products, clinical investigation protocol concerning a medical device or interventional protocol not concerning a health product, or in the exclusion period any other interventional study
27. Pregnancy or desire for pregnancy or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of success at week 48. Success is defined as patients with serum ALP <1.3 ULN at week 48 and a reduction of, at least 15%, compared to baseline ALP level AND total bilirubin ≤ 1 ULN at week 48

Secondary endpoints 13

1. Proportion of patients with serum ALP <1.3 ULN and a reduction of at least 15% compared to baseline ALP level at week 12 24 36 and 48
2. Proportion of patients that normalized total bilirubin at week 12 ,24 36 and 48 (total bilirubin <1 ULN)
3. Proportion of patients that normalized ALP at week 12 24 36 and 48 (ALP <1 ULN)
4. Proportion of patients that normalized all liver tests (ALP <1ULN and GGT <1 ULN and AST <1 ULN and ALT <1 ULN and total bilirubin <1 ULN) at week 12 24 36 and 48
5. Change in Elastometry between week 0 and week 48
6. PSC Prognostic scores including the MELD score, the Revised PSC Mayo Risk Score, the Amsterdam-Oxford prognostic model (week 0, week 24, week 48)
7. Safety endpoints: - Percentage of patients with clinical (including infectious events and increased IBD activity) or biological adverse events (leucocytes, CRP) during the study period (overall and between randomization and week 48, between randomization and week 104) - Survival rate without liver events (decompensation of cirrhosis, acute cholangitis, jaundice, need for ERCP) at week 48
8. Pruritus (VAS and 5D pruritus scale) at week 0, 12, 24, 36 and 48
9. Symptoms and quality of life (PRO-CSP questionnaire, QMCF questionnaire – Questionnaire de la maladie chronique du foie) and fatigue (PBC 40 questionnaire) : at week 0, week 24 and week 48
10. Bile acids measured by chromatography at week 0, week 48
11. Cholangiographic abnormalities, assessed by magnetic resonance cholangiography at week 0, week 48
12. Changes in IBD activity: clinical score between week 0 and week 48 (HBI and Crohn’s disease Activity Index [CDAI] for Crohn’s disease and Mayo score for Ulcerative colitis), fecal calprotectin and endoscopic score assessed by colonoscopy (Crohn’s disease Endoscopic Index of Severity [CDEIS] for Crohn’s disease and ulcerative colitis Endoscopic Index of Severity [UCEIS] for ulcerative colitis).
13. Analysis of gut microbiota at week 0, 12, 24, 36 and 48.

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

stanislas quenard

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

stanislas quenard

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Results and documents

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

Documents 22 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