Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)®

A Phase 2a, Open-label, Randomized, Controlled, Multi-center Proof of Concept Study to Assess the Efficacy, Safety, and Tolerability of VS-01 on Top of Standard of Care, Compared to Standard of Care Alone, in Adult Patients With Acute-on-chronic Liver Failure (ACLF)

A Phase 2, multi-center, randomized, controlled, open-label study to evaluate the effects of the intraperitoneal, liposomal formulation VS-01 in patients with an acute episode of hepatic and/or extrahepatic organ dysfunctions and failures in the presence of liver cirrhosis (Acute-on-Chronic Liver Failure, ACLF) and accumulation of fluid in the abdominal cavity (ascites)

Inclusion Criteria:

1. Patients with ACLF Grade 1, 2, or 3a according to European Association for the Study of the Liver (EASL)-CLIF criteria;
2. Onset of ACLF not more than 14 days before Baseline (BL);
3. Presence of ascites requiring diagnostic or therapeutic paracentesis;
4. Patients with dry body weight ≥40 and <140 kg;
5. Written informed consent obtained prior to the start of any study-related procedures.

Exclusion Criteria:

1. Presence of any of the following organ failure(s) as per the EASL-CLIF criteria and/or adapted from CLIF-C Organ Failure (CLIF-C OF)/CLIF- Sequential Organ Failure Assessment (CLIF-SOFA) scores:

   1. Respiratory failure necessitating invasive mechanical ventilation;
   2. Coagulation failure (INR > 3.2 or platelet count ≤20 x 109/L);
   3. Severe cardiovascular failure requiring the use of high dose vasopressors;

2. ACLF grade 3b: Presence of four or more organ failures as per EASL CLIF criteria;

3. Presence of spontaneous or secondary bacterial peritonitis;

4. Presence of uncontrolled severe infection(with hemodynamic instability or shock);

5. Poorly controlled seizure disorder;

6. Patients with history of upper gastro-intestinal bleeding over the past 7 days prior to BL, acute bleeding or bleeding upon paracentesis at screening (SCR) or BL;

7. Contraindication for paracentesis;

8. Coagulation disorders such as disseminated intravascular coagulation or hemophilia;

9. Potential or known hypersensitivity to liposomes;

10. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities;

11. Patients after organ transplantation receiving immunosuppressive medication;

12. Any severe disease considered to be potentially detrimental at the discretion of the Principal Investigator. 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. Need for Renal Replacement Therapy or any extracorporeal liver support device (e.g., MARS®, Prometheus®, plasmapheresis);

14. Alfapump® in place to manage ascites;

15. Pregnancy and lactation;

16. Women of child-bearing potential who are not willing to use adequate contraception;

17. Patients who participate in another clinical trial at the time of SCR or within 4 weeks prior to SCR.