Encapsulated faecal microbiota transfer to target immune activation in patients with cirrhosis and ascites (TransImmune): protocol for a randomised, double-blind, Phase IIa, placebo-controlled trial

INTRODUCTION: Bacterial translocation and gut dysbiosis are key drivers of systemic immune activation in decompensated cirrhosis, precipitating inflammatory complications such as acute-on-chronic liver failure (ACLF). Currently, no licensed therapies effectively restore intestinal barrier function or reverse dysbiosis in this vulnerable population. While previous studies have suggested benefits of faecal microbiota transfer (FMT) in hepatic encephalopathy or alcohol-associated hepatitis, data on its safety and immunomodulatory effects in decompensated cirrhosis with ascites are lacking. This Phase IIa trial (TransImmune) aims to evaluate the safety and tolerability of encapsulated FMT. Furthermore, it will assess feasibility, microbial engraftment and downstream effects on intestinal barrier integrity, as well as systemic and peritoneal inflammation. METHODS AND ANALYSIS: This is a prospective, single-centre, randomised, double-blind, placebo-controlled Phase IIa pilot study. A total of 24 patients with decompensated cirrhosis and ascites will be randomised in a 1:1 ratio to receive either encapsulated FMT or placebo over three consecutive days. The investigational product, INTESTIFIX 001, is an encapsulated FMT preparation derived from rigorously screened healthy donors and manufactured under Good Manufacturing Practice (GMP) conditions with predefined release specifications, including minimum alpha-diversity QC criteria, manufactured by the Cologne Microbiota Bank (CMB). The primary endpoints are the occurrence of serious adverse events (SAE) up to the end of study (EOS) and the occurrence and severity of treatment-emergent adverse events (TEAE). Secondary endpoints evaluate signals of clinical efficacy, specifically: (1) systemic inflammation (white blood cell count, C-reactive protein, procalcitonin and IL-6); (2) gut inflammation (faecal calprotectin); (3) organ dysfunction (Child-Pugh, MELD and CLIF-SOFA scores); (4) quality of life (EQ-5D-5L and CLDQ) and (5) the number of antibiotic-free days. Patients will be monitored across five study visits up to 90 days. ETHICS AND DISSEMINATION: The study was approved by ethics committee review and the German Federal Institute for Drugs and Medical Devices (BfArM). The trial is registered under EU CT no. 2023-5 07 790-18-00. The results of the study will be disseminated via peer-reviewed publications and at international conferences. TRIAL REGISTRATION NUMBER: EU Clinical Trials Register: 2023-507790-18-00. Registered on 8 August 2024.