Liver cirrhosis and hepatic encephalopathy Digestive System
Conditions
Interventions
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
Sponsors
EnteroBiotix Limited
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 31/10/2025: 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], 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. 4. (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. Subjects taking rifaximin should be stable at the prescribed dose for at least 4 weeks prior to randomisation. 5. 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. 6. Willing to abstain from consuming regular ‘over the counter’ pre or probiotics from pharmacies or other retailers from screening through to Week 12 after treatment. Food products such as cheese, yoghurts, fermented pickles and probiotic drinks from the food section of supermarkets are acceptable. 7. Subjects with an alcohol use disorder should be willing to abstain from alcohol during the screening, treatment and follow up period. Where subjects do not have an alcohol use disorder, alcohol may be consumed within the National Health Service (NHS) guidelines of =14 units per week, spread over at least 3 days per week. 8. Subjects with any other substance use disorder should be willing to abstain from those and other related substances, including substitutes, during the screening, treatment and follow up period. Stable cannabis use is permitted in the absence of overt intoxication at screening and randomisation. Stable opiate substitutes (eg. methadone) are permitted providing bowel habits are usually regular, where regular is defined as a bowel movement at least every other day. 9. Subjects with any substance or alcohol use disorder must have abstained from substance use for =3 months prior to screening. 10. If women of child-bearing potential (WOCBP), subjects must have a negative serum pregnancy test at screening and randomisation and must be willing to use a highly effective method of birth control for the duration of the study. Acceptable methods of contraception: 10.1. Hormonal contraception associated with inhibition of ovulation 10.2. Intrauterine device (IUD) 10.3. Intrauterine hormone-releasing system (IUS) 10.4. Bilateral tubal occlusion 10.5. Vasectomised partner 10.6. Sexual abstinence, in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 11. If male, subjects must be prepared to use reliable barrier method contraception and a second method such as spermicide for the duration of the study unless surgically sterile. Condom with spermicide is not considered a highly effective method of contraception for female subjects of child-bearing potential. 12. Willing and able to comply with all study requirements _____ Previous key 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] o
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 31/10/2025: 1. Women who are pregnant or breastfeeding 2. OHE as defined by Grade =2 WHG within 1 month of screening. 3. Part A only: any prior episode of HE 4. Overnight admission to hospital with OHE or any other liver-related complication, or any other non-elective admission to hospital, within the 4 weeks prior to screening. 5. Planned surgery requiring general anaesthetic during the course of the study. 6. History of total colectomy/ileostomy at any time, or bariatric/gastric surgery in the last 2 years. 7. Any other major intra-abdominal surgery within 60 days prior to screening 8. Confirmed diagnosis of Wernicke’s Encephalopathy (WE) at any time prior to screening (prophylaxis of WE at any time prior to or during the study in accordance with the standard of care, with no confirmed diagnosis is permitted) 9. Korsakoff’s Disease at any time prior to screening. 10. Confirmed diagnosis of dementia of any aetiology 11. Clinical signs and symptoms of dehydration at screening or baseline. 12. Any ongoing underlying issues which increase the risk of an OHE episode (e.g. unresolved gastrointestinal [GI] bleed; ongoing bacterial infection) at screening or baseline. 13. Diarrhoea of any aetiology within 7 days prior to screening. 14. Any anti-diarrhoeal or anti-peristaltic medication within 7 days prior to screening 15. Medications for HE 15.1. – Part A: medications for HE, including but not limited to lactulose, rifaximin, LOLA, BCAAs or other antibiotics. Rifaximin use for other conditions is also excluded. 15.2. – Part B: Part B: Medications for hepatic encephalopathy, including but not limited to: LOLA, BCAAs or antibiotics other than rifaximin within 3 months prior to screening. Lactulose is mandated. 16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =4 x ULN 17. Planned organ transplant during the study period. 18. Chemotherapy, radiotherapy or immunotherapy within 3 months prior to baseline, or planned during the study 19. Life expectancy <4 months 20. Ongoing infectious hepatitis (A, B or C) or recent history that has not fully resolved at least 3 months prior to screening 21. Any other known immunodeficiency, including human immunodeficiency virus (HIV) with CD4+ T-cell counts <500 cells/mm3 22. Known gastrointestinal disease, including but not limited, to ulcerative colitis, Crohn’s disease, coeliac disease, indeterminate colitis or microscopic colitis, diverticulitis. 23. No bowel movement (constipation) within 3 days prior to study drug administration. 24. Use of systemic antibiotics within 7 days prior to screening, or intended use during the study, with the exception of stable rifaximin for Part B subjects. 25. Patients receiving total parenteral or enteral nutrition. Nutritional supplements are permitted, with the exception of non-food pre- or probiotics. 26. Any autoimmune disease requiring, or that may require, systemic treatment with steroids and/or other immunosuppressants/immunomodulators and/or biological agents including SLE, RA, psoriatic arthritis and connective tissue disorders and MS. Autoimmune hepatitis is also excluded. Subjects with mild autoimmune disease not requiring systemic treatment, including vitiligo and alopecia areata, may be included. 27. Use of systemic steroids within the previous four weeks (inhaled and topical steroids are acceptable). 28. Uncontrolled Type I or Type II diabetes mellitus that has required hospitalisation within the last
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of EBX-102 measured using the incidence of adverse events, serious adverse events at week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed