Multicenter, prospective, double-blind, randomized, three-armed, placebo-controlled study of long-term therapeutic transfer of encapsulated stool microbiome for the treatment of active ulcerative colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Friedrich-Schiller-Universitaet Jena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

26 Jan 2023 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517132-22-00

EudraCT number

2019-000259-15

ClinicalTrials.gov

NCT03843385

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

clinical efficacy of long-term transplantation of capsules with faecal microbiota and faecal microbiota filtrate

Conditions and MedDRA coding

active ulcerative colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. • Age between 18 and 75 years
2. • written consent
3. • prior endoscopic confirmation of colitis ulcerosa (first diagnosis of at least 6 months, active disease: mayo score between 4-10 points at screening, documented endoscopic minimum disease extent of 15 cm from the anal verge (mayo endoskopic subscore >1)
4. • Failure of conventional therapy or treatment with biologicals and/or small molecules
5. • previous medical therapy: -oral 5-ASA compounds (5-ASA) (stable dose for 4 weeks before randomisation) OR -Azathioprine, 6-MP or MTX (stable dose for 8 weeks before randomisation) OR -oral steroid therapy: (prednisone (≤ 20 mg/day) or budesonide (≤ 9 mg/day)) (stable dose for 2 weeks before randomisation) OR -topical therapy (foams, clysms) with mesalazine or budesonide (stable dose for 2 weeks before randomisation)
6. • previous vaccination against SARS-CoV-2 or previous SARS-CoV-2 infection or positive serology
7. • Ability to understand study procedures and willingness to meet requirements associated with participation (e. g. endoscopy, intake antibiotics)
8. • potentially childbearing patient: negative pregnancy test and use of a highly effective contraceptive method

Exclusion criteria 22

1. • Crohn´s disease, indeterminate colitis or ulcerative proctitis (< 15 cm ab ano)
2. • Acute abdomen or other clinical emergencies (toxic megacolon, fulminant gastrointestinal hemorrhage, ileus, perforation, etc.)
3. • Previous operations on the colon: colectomy, partial colon resections
4. • current gastrointestinal infections (e. g. Clostridium difficile infection, CMV infection) until randomisation
5. • Congenital or acquired immunodeficiency
6. • severe comorbidity (e.g. insulin-dependent diabetes mellitus, decompensated liver cirrhosis, primary sclerosing cholangitis, renal impairment > grade 2)
7. • diagnosis of a malignoma in the last 3 years
8. • refusal of endoscopies with video documentation
9. • No specific therapy for ulcerative colitis to date
10. • lack of immunity to SARS-CoV-2
11. • Previous treatment with TNF-, IL12/IL23-, IL23- or integrin-antibodies (8 weeks before randomisation)
12. • Treatment with calcineurin inhibitors (4 weeks before randomization)
13. • Treatment with JAK inhibitors (e.g., tofacitinib, filgotinib, or upadacitinib) (4 weeks before randomization)
14. • Treatment with S1P receptor modulator (e. g. ozanimod, etrasimod) (4 weeks before randomization)
15. • Systemic antibiotic treatment (8 weeks before randomization)
16. • Known intolerance to metronidazole or vancomycin
17. • Participation in a clinical trial (3 months before randomization)
18. • Previous FMT or FMFT, previous participation in this study (screening allowed)
19. • Use of probiotics in tablet, capsule, or powder form, or appropriate drinking yogurts (or similar) (2 weeks before randomization)
20. • Failure to ensure frozen storage of investigational products: no possibility to store capsules at ≤ -10°C, planned longer absence (12 weeks after randomization)
21. • Addictive or other medical conditions or circumstances that do not allow the subject to appreciate the nature, significance, scope, and possible consequences of the clinical trial
22. • Indications that the patient would be unlikely to comply with the protocol (e.g., unwillingness to cooperate - compliance questionable)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. clinical remission at week 12 post transfer defined by Mayo score ≤ 2 and any subcore ≤ 1, missing values to week 12 are considered as no remission

Secondary endpoints 9

1. - steroid-free clinical remission
2. - Mayo score
3. - endoscopic remission
4. - clinical response
5. - mucosal infammation (fecal calprotectin)
6. - histological mucosal inflammation (Nancy index)
7. - quality of life
8. - microbiome and virome analysis
9. - safety

Investigational products

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

Test 2

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Friedrich-Schiller-Universitaet Jena

Sponsor organisation

Friedrich-Schiller-Universitaet Jena

Address

Am Klinikum 1, Lobeda Lobeda

City

Jena

Postcode

07747

Country

Germany

Scientific contact point

Organisation

Friedrich-Schiller-Universitaet Jena

Contact name

Prof. Dr. Andreas Stallmach

Public contact point

Organisation

Friedrich-Schiller-Universitaet Jena

Contact name

Prof. Dr. Andreas Stallmach

Locations

1 EU/EEA country · 21 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 6 files

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

Application history

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