A Randomized controlled open-label phase II trial assessing the efficacy and safety of two-dosing regimens of frozen encapsulated fecal microbiota transfer products with or without an individualized donor selection approach in decolonizing carriers of multi-drug resistant Enterobacteriaceae (RESET-MDR)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Goethe University Frankfurt

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

23 Jan 2026 → ongoing

Decision date (initial)

2025-05-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of an antibiotic induction regimen in combination with high-dose individualized oral encapsulated fecal microbiota transfer (FMT) in achieving eradication of multidrug resistant Enterobacteriaceae (MDR-E) at day 30

Secondary objectives 8

1. • To assess the safety and tolerability of an antibiotic induction regimen in combination with encapsulated individualized FMT
2. • To assess the potential added value of an FMT dose intensification from single to double FMT administration
3. • To assess the potential benefits of an individualized FMT compared to standard FMT
4. • To assess the potential of FMT in preventing bacterial infections
5. • To assess the potential of FMT in preventing any type of infection (bacteria, viruses, fungi, parasites)
6. • To assess the potential of FMT to prevent further infection episodes in patients with recurrent MDR-E infections
7. • To assess the potential of FMT in preventing hospitalizations due to any kind of complication
8. • To assess the effect of FMT on all-cause mortality

Conditions and MedDRA coding

Infections with multidrug-resistant Enterobacteriaceae

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Patients aged ≥ 18 years
2. 2. Fecal colonization with an MDR-E, fulfilling the criteria for classification as 3MRGN or 4MRGN (as defined by the Robert-Koch-Institute) confirmed by a positive sample (rectal swab or stool sample) obtained within 14 days prior to study enrolment
3. 3. Patients at risk of infection with the colonizing strain referred to in criterion 2 (based on cultural resistance testing) who already experienced at least two infections within the last 6 months or three infections within the last 12 months prior to enrolment. AND/OR Patients under moderate mid- or long-term immunosuppression, defined by ≥ 1 of the following criteria: a) solid organ transplant recipients receiving ≥ 2 immunosuppressants b) recipients of CAR-T-cell therapy or hematopoietic stem cell transplantation either within 100 days to 2 years of CAR-T-cell/ stem cell infusion c) moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome) d) Use of at least 1 of the following medications: i. Recent treatment with corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days, all of which must have been within the last 30 days prior to study entry OR are currently receiving ≥20 mg daily that must have been administered for at least 14 consecutive days at the time of study entry. ii. Active treatment causing significant immunosuppression, including alkylating agents, antimetabolites, transplant-related immunosuppressive or immunomodulatory drugs (e.g. cyclosporin A, tacrolimus, methotrexate, mycophenolat mofetil, anti-T-cell immunoglobulin, everolimus, sirolimus, ruxolitinib, basiliximab, vedolizumab, cyclophosphamide), cancer chemotherapeutic agents, TNF blockers, or immunomodulatory drugs (e.g. monoclonal antibodies, bispecific antibodies, checkpoint inhibitors, biologics, Janus kinase inhibitors) e) chronic kidney diseases stage (CKD-EPI stage 4 or 5) requiring chronic hemodialysis for at least 6 months f) HIV infection with CD4+ cell count <200/mm³ from known medical history within the past 6 months of screening.

Exclusion criteria 13

1. 1. Resistance to colistin according to EUCAST breakpoints v.12 (MIC > 2 mg/L) of the MDR-E isolate at baseline
2. 10. Current pregnancy or nursing period
3. 11. Failure to use highly-effective contraceptive methods
4. 12. Inability to give written informed consent
5. 2. Foreseeable inability to swallow 30 FMT capsules over two days
6. 3. Active inflammatory bowel disease (e.g. ulcerative colitis or Crohn’s disease)
7. 4. Severe immunosuppression defined as: (a) patients with current or foreseeable neutropenia within the 14 days of study treatment (defined as <500 neutrophils/µl) (b) patients scheduled for allogeneic stem cell transplantation (SCT) or having received allogeneic SCT within the 100 days prior to study treatment (c) patients with active graft versus host disease or allograft rejection requiring intensified immunosuppressive treatment, defined as the current use of >2 immunosuppressive or immunomodulatory drugs (e.g. cyclosporin A, tacrolimus, methotrexate, mycophenolat mofetil, anti-T-cell immunoglobulin, everolimus, sirolimus, ruxolitinib, basiliximab, vedolizumab, corticosteroids or cyclophosphamide)
8. 5. Active infection with the MDR-E organism to be eradicated
9. 6. Current or scheduled administration of antibiotic treatment active against the MDR-E organism to be eradicated
10. 7. Planned selective digestive tract decolonization within 30 days following randomization
11. 8. Known hypersensitivity or allergy to any of the components of the study treatment
12. 9. Current hospitalization in an Intensive Care Unit
13. 13. Concurrent participation in another clinical trial with an investigational drug is not permitted, unless the drug under study is related to the treatment of the underlying condition or a transplantation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Detectable intestinal carriage of MDR-E at day 30 in standard qualitative cultural assessment

Secondary endpoints 8

1. • Comparison of safety and tolerability data between groups via review of nature, frequency and severity of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 30 days
2. • Characterization of changes in bacterial and fungal intestinal microbiota community structures and taxonomic classification (α- and ß-diversity) at day 0 compared to day 4, 12, 30 and 90
3. • Comparison of intestinal carriage of MDR-E at day 30 in quantitative cultural assessment
4. • Characterization and differences of patterns in the intestinal microbiota distribution in patients at baseline compared to day 4, 12, 30 and 90 with and without successful decolonization
5. • Rate of bacterial infections until day 90
6. • Rate of MDR-E infections until day 90
7. • Rate of any type of infection (bacteria, viruses, fungi, parasites) until day 90
8. • Rate of hospitalization and all-cause mortality until day 90

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Goethe University Frankfurt

Sponsor organisation

Goethe University Frankfurt

Address

Theodor-Stern-Kai 7

City

Frankfurt Am Main

Postcode

60590

Country

Germany

Scientific contact point

Organisation

Goethe University Frankfurt

Contact name

Maria Vehreschild

Public contact point

Organisation

Goethe University Frankfurt

Contact name

Maria Vehreschild

Locations

1 EU/EEA country · 6 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 24 files

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

Application history

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