Sponsor decision

A Phase 2, Randomized, Controlled, Open-Label, Adaptive Dose Design, Proof-of-Concept Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Two Different Dwell Times of VS-01 on Top of Standard of Care versus Standard of Care Alone in Patients with Overt Hepatic Encephalopathy

Inclusion Criteria:

• 1)Patients with liver cirrhosis of any underlying etiology (liver cirrhosis diagnosed by standard clinical criteria, imaging findings and/or histology), who are diagnosed with Overt hepatic encephalopathy (OHE) (according to Hepatic Encephalopathy Grading Instrument) in the presence of:

  1. Acute decompensation (AD)(defined as the onset or worsening of ascites, hepatic encephalopathy, gastrointestinal (GI) bleeding or any combination of them with or without infection); or
  2. Acute on chronic liver failure (ACLF) grade 1 according to European Association for the Study of the Liver(EASL-CLIF) criteria; 2)Presence of ascites requiring diagnostic or therapeutic paracentesis; 3)Fasting blood ammonia > upper limit of normal (ULN) at baseline (BL); 4)Patients with a dry body weight ≥40 kg and <140 kg; 5)Male and female patients ≥18 to <80 years of age on the day of signing the informed consent form (ICF); 6)Patients willing and able to provide written informed consent. If the patient is unable to fully understand or sign the written informed consent based on the Investigator's judgment, the ICF must be signed by a legal representative of the patient according to local regulation.

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.