A Study to See if an Investigational Medicine Called VS-01 Can Help and How Safe it is in the Treatment of Patients With Overt Hepatic Encephalopathy

Exclusion Criteria

• •1. ACLF grade 2 or higher as defined by European Association for the Study of the Liver-Chronic Liver Failure-Chronic Liver Failure (EASL-CLIF) criteria;
• •2. Presence of spontaneous or secondary bacterial peritonitis (i.e., neutrophil counts \>250/mm3 in ascitic fluid);
• •3. Contraindication for paracentesis according to the European Association for the Study of the Liver (EASL) Clinical Practice Guidelines 2018, and American Association for the Study of Liver Diseases (AASLD)Guideline on the Treatment of Ascites, Spontaneous Bacterial Peritonitis, and Hepatorenal Syndrome 2021;
• •4. Alfapump® in place to manage ascites;
• •5. Known hypersensitivity to liposomes, history of mastocytosis, multiple hypersensitivities or similar diseases known to be associated with an increased risk of allergic/anaphylactoid reactions;
• •6. Upper GI bleeding within the last 7 days prior to BL, acute bleeding or bleeding upon paracentesis at Screening (SCR) or Baseline (BL);
• •7. Poorly controlled seizure disorder;
• •8. Respiratory failure requiring invasive mechanical ventilation;
• •9. Severe circulatory failure requiring the use of high dose vasopressors (e.g., dopamine \>15 μg/kg/min, or epinephrine \>0.1 μg/kg/min, or norepinephrine \>0.1 μg/kg/min); the use of terlipressin or low-dose norepinephrine to treat hepatorenal syndrome is not an exclusion criterion;
• •10. Uncontrolled severe infection with hemodynamic instability or shock; patients may be enrolled provided anti-infectives have been administered for at least 48 hours prior to BL with an appropriate response as assessed by the Principal Investigator (PI);
• •11. Need for Renal replacement therapy (RRT) or any extracorporeal liver support device;
• •12. Any significant disease considered to be potentially detrimental or would preclude the patient from participating in and completing the study as assessed by the PI. This includes but is not limited to hepatocellular carcinoma outside Milan criteria, cholangiocarcinoma, extrahepatic cancer over the past 2 years, or people who inject drugs;
• •13. Individuals for whom the PI deems that study participation would be unsafe or not in the interest of the patient;
• •14. Pregnancy or lactation;
• •15. Women of childbearing potential and non-sterile male patients who are not willing to use adequate contraception from SCR to 30 days after the final dose of investigational medicinal product (IMP);
• •16. Participation in another interventional clinical trial within 30 days of SCR.