FMT in Checkpoint Inhibitor-mediated Diarrhea and Colitis (Immunobiome)

Faecal Microbiota Transplantation for Immune Checkpoint Inhibitor-mediated Diarrhea/Colitis: a Randomised, Double-blind Pilot Efficacy and Safety Study

The goal of this clinical trial is to determine the outcome of patients with immune checkpoint inhibitor-mediated diarrhea/colitis (IMC) treated with faecal microbiota transplantation (FMT) in a randomised, placebo-controlled trial.

The aim of the present study is to assess the feasibility, pilot efficacy, and safety of FMT for patients with IMC.

Participants will be treated two times with capsule FMT or placebo capsules in a 1:1 ratio. The intervention treatment will be an add-on to the patients' standard treatment for IMC.

Researchers will compare the FMT-treated group to the placebo-treated group to see if FMT promotes remission of IMC.

Study Overview

• Status: Recruiting
• Conditions: Kidney Cancer; Diarrhea; Colitis; Malignant Melanoma
• Intervention / Treatment: Procedure: Faecal Microbiota Transplantation (FMT); Procedure: Placebo

Detailed Description

As above

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian L Hvas, PhD; Phone Number: +4528351839; Email: christian.hvas@auh.rm.dk
• Study Contact Backup: Name: Trine L Laursen, BSc; Phone Number: +4540408207; Email: trnlau@rm.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Christian L Hvas, PhD; Phone Number: +45 28351839; Email: christian.hvas@auh.rm.dk
    • Contact: Trine L Laursen, BSc; Email: trnlau@rm.dk
    • Sub-Investigator: Trine L Laursen, BSc
    • Principal Investigator: Christian L Hvas, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or above.
2. Histologically proven diagnosis of malignant melanoma and/or kidney cancer.
3. Treatment with any immune checkpoint inhibitor (Nivolumab, Pembrolizumab, Cemiplimab, Atezolizumab, Durvalumab, Avelumab, Ipilimumab), alone or in combination, within the last 8 weeks.
4. Grade 2 or higher CTCAE diarrhea, of which at least 3 stools are Bristol chart score 6-7.
5. Negative PCR for enteric pathogens including C. difficile, after the onset of diarrhea.
6. Signed written informed consent.

Exclusion Criteria:

1. Diagnosed bacterial infection requiring antibiotic treatment at inclusion.
2. Pregnancy or breastfeeding. Pregnancy ruled out by male sex, postmenopausal women or a negative choriogonadotropin (hCG) urine test.
3. Primary diarrheal disease pre-existing to the immune checkpoint inhibitor treatment, including inflammatory bowel disease.
4. Unable to ingest capsules.
5. Unable to understand written or oral patient information.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Faecal microbiota transplantation (FMT); Patients receive two applications of capsule FMT with 3-7 days between applications.	Procedure: Faecal Microbiota Transplantation (FMT); Capsule FMT; Other Names: FMT; Fecal Microbiota Transplantation
Placebo Comparator: Placebo; Patients receive two applications of placebo capsules with 3-7 days between applications.	Procedure: Placebo; Placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission of immune-mediated diarrhea	Number of patients with steroid-free resolution of diarrhea, defined as < 3 liquid stools (Bristol <6) per 24 hours during day 40 and 41 after the last intervention treatment.	At 42 days after intervention treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission of diarrhea defined by CTCAE	Number of patients in steroid-free clinical remission of diarrhea 6 weeks (42 days) after the last intervention treatment. Clinical remission is defined as < 4 stools over baseline per day (CTCAE diarrhea grade 1 or less), at day 40 and 41.	At 42 days after intervention treatment
Remission of colitis defined by CTCAE	Number of patients in steroid-free clinical remission of colitis 6 weeks (42 days) after the last intervention treatment. Clinical remission is defined as asymptomatic in regards to colitis (CTCAE colitis grade 1 or less), at day 40 and 41.	At 42 days after intervention treatment
Therapy response of FMT	Therapy response defined as a decrease of at least 3 points in Simple Clinical Colitis Activity Index (SCCAI) score, at weeks 1, 6 and 12 after the last intervention treatment.	Up to 12 weeks after intervention treatment
Number of days until CTCAE diarrhea grade 1	Number of days until less than 4 stools over baseline per day (CTCAE diarrhea grade 1 or less), lasting a minimum of 48 consecutive hours with no increase in steroid dose in the 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Number of days until resolution of diarrhea	Number of days until resolution of diarrhea, defined as 3 or fewer Bristol type 6-7 stools per day, lasting a minimum of 48 consecutive hours.	Up to 12 weeks after intervention treatment
Incidence of fecal microbiota transplantation (FMT)-related adverse events	Number of adverse events (AE) during first 6 weeks after intervention treatment. AE's will be graded by CTCAE.	At 42 days after intervention treatment
Incidence of fecal microbiota transplantation (FMT)-related serious adverse events	Number of serious adverse events (SAE) during 12 weeks follow-up after the final intervention treatment. SAE's will be graded by CTCAE.	At 12 weeks after intervention treatment
Faecal microbiota composition	Changes in faecal microbiome composition from baseline to week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Gut mucosa-associated microbiome	Changes in mucosa-associated microbiome from baseline to week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Faecal-calprotectin	Percentual change in faecal-calprotectin from prior to intervention to week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Blood immunological parameters	Changes in blood immunological parameters (including circulating cytokines) from baseline and at week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Hospitalisation	Hospitalisation defined as the total number of days hospitalised, during 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Colectomy	Colectomy during 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Mortality	Mortality during the 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Accumulated steroid dose	Accumulated steroid dose (total dose in mg) during 12 weeks following experimental treatment.	Up to 12 weeks after intervention treatment
Resumption of immune checkpoint inhibitor therapy	Number of patients resuming immune checkpoint inhibitor therapy during the 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Response to immune checkpoint inhibitor therapy	Response to immune checkpoint inhibitor therapy defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1 and iRECIST).	Up to 12 weeks after intervention treatment
Patient and physician perceptions of FMT treatment	Patient and physician perceptions of FMT treatment and the usage for IMC assessed by a patient questionnaire at week 6 and a physician questionnaire.	At 42 days after intervention treatment
Health-related quality of life	Changes in health-related quality of life assessed by EQ-5D-5L at baseline and week 6.	At 42 days after intervention treatment
Endoscopic response	Endoscopic response, defined as decrease in Mayo endoscopic score ≥1 grade, at week 6 after the last intervention treatment.	Up to 6 weeks after intervention treatment
Endoscopic remission	Endoscopic remission, defined as Mayo endoscopic score 0, at week 6 after the last intervention treatment.	Up to 6 weeks after intervention treatment

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Christian L Hvas, PhD, University of Aarhus

Publications and helpful links

Helpful Links

• Centre for faecal microbiota transplantation (CEFTA)

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Signs and Symptoms, Digestive; Intestinal Diseases; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Skin Diseases; Gastroenteritis; Urologic Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Colitis; Melanoma; Kidney Neoplasms; Diarrhea; Therapeutics; Biological Therapy; Fecal Microbiota Transplantation
• Other Study ID Numbers: 1-10-72-105-23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Open access publication, raw data available upon reasonable request and according to data protection regulation.
• IPD Sharing Time Frame: Protocol: On request. Other: after study completion
• IPD Sharing Access Criteria: Evaluated after email request, trnlau@rm.dk
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No