A multicentre, randomised, double-blind placebo-controlled, phase II study to evaluate the safety, tolerability and dose of dried intestinal microbiota medicinal product EBX-102 in liver cirrhosis subjects (IMPuLCE)

INTERVENTION: This is a phase II (first‐in‐human), multicentre, randomised, double‐blind, placebo‐controlled study. Trial Arms: The study consists of two parts (A and B). Part A (Dose escalation) will involve two cohorts of approximately 12 subjects (n=24) with liver cirrhosis (MELD‐Na score <12) without hepatic encephalopathy (HE) and who are not taking medications for Hepatic Encephalopathy (HE). Part B (Dose Expansion): Will involve approximately 32 subjects with liver cirrhosis (MELDNa score 12 ‐16), with or without minimal hepatic encephalopathy (MHE), and who are receiving treatment At the end of Part A, a Dose Selection Review (DSR) meeting will occur to determine the dose for part B. Randomisation: Will be via IWRS. In Part A, in the first two cohorts, patients will be randomised at a ratio of 2:1 active: placebo) to assess the optimal dose regimen (n=24). Part B will consist of 32 subjects with a 5:3 randomisation active: placebo. Dose/Dose Range/Frequency: EBX‐102 will be given as a single dose, soon after randomisation under strict observation and thereafter participants are followed for 12 weeks to assess safety, tolerability and microbiota dynamics. The dose will depend on the part and cohort of the study the patient is randomised to. Route of administration: Oral Administration CONDITION: Liver cirrhosis and hepatic encephalopathy ; Digestive System PRIMARY OUTCOME: Safety and tolerability of EBX‐102 measured using the incidence of adverse events, serious adverse events at week 12 SECONDARY OUTCOME: Changes in intestinal microbiota taxonomic composition (bacterial diversity and relative abundance) measured using 16SrRNA sequencing of stool samples at week 1, week 4, week 8 and week 12 post‐treatment INCLUSION CRITERIA: 1. Willing and able to provide informed consent 2. Male or female aged =18 years 3. A clinical diagnosis of LC, as confirmed by confirmatory scan (magnetic resonance imaging [MRI], 4. ultrasound, computed tomography [CT] or transient elastography) and/or needle biopsy of the liver. A needle biopsy is not a mandated procedure for study purposes. 5. (Part B only) Must be clinically stable on lactulose as deemed by the investigator for at least 1 month prior to randomisation, with the intent to remain on stable dose of treatment throughout the study period. Small daily variations of lactulose are permitted and must be recorded. 6. Subjects taking rifaximin should be stable at the prescribed dose for at least 4 weeks prior to randomisation. 7. MELD‐Na score: 5.a ‐ Part A: MELD‐Na score of <12 5.b ‐ Part B: Minimum MELD‐Na score of 12 and a maximum MELD‐Na score of 16. 8. Willing to abstain from consuming regular ‘over the counter’ pre or probioti