VS-01 in Acute-On-Chronic Liver Failure

What is the Purpose of this Study?

The purpose of this study is to determine whether an investigational drug called VS-01 will help in the treatment of acute-on-chronic liver failure (ACLF) grades 1 and 2 with fluid in the abdomen (ascites). ACLF is a potentially life-threatening complication in patients with cirrhosis that is characterized by multi-organ dysfunction. Study procedures include blood draws, electrocardiogram, removal of fluid from the abdomen, and administration of the drug. VS-01 is an experimental medicine that helps to remove ammonia from the body. It also potentially helps to remove metabolites (substances that the body may produce) that are involved in the development and progression of ACLF. VS-01 comes in a liquid form containing free citric acid and lipid droplets made of fatty substances that may naturally occur in human bodies. VS-01 will be administered into the abdominal cavity using a standard flexible tube routinely used for removal of abdominal fluid (ascites). Participants will be in the active treatment group and will receive VS-01 together with the standard of care, or they will be placed in the control group and will receive standard of care only.

Eligibility

1. Patients with liver cirrhosis diagnosed by standard clinical criteria, imaging findings and/or histology with any underlying etiology;
2. Patients with liver cirrhosis with ACLF Grade 1 or 2 according to European Association for the Study of the Liver (EASL)-CLIF criteria as described in the EASL-Clinical Practice Guideline on acute-on-chronic liver failure (EASL Clinical Practice Guidelines, 2023);
3. Onset of ACLF not more than7 days (168 hours) before Baseline;
4. Presence of ascites requiring paracentesis;

Inclusion Criteria:

1. Patients with liver cirrhosis diagnosed by standard clinical criteria, imaging findings and/or histology with any underlying etiology;
2. Patients with liver cirrhosis with ACLF Grade 1 or 2 according to European Association for the Study of the Liver (EASL)-CLIF criteria as described in the EASL-Clinical Practice Guideline on acute-on-chronic liver failure (EASL Clinical Practice Guidelines, 2023);
3. Onset of ACLF not more than7 days (168 hours) before Baseline;
4. Presence of ascites requiring paracentesis;
5. Patients with dry body weight ≥ 40 and \<140 kg;
6. Written informed consent obtained prior to the start of any study-related procedures.

Exclusion Criteria:

1. Patients with acute or sub-acute liver failure;
2. Presence of the following organ(s) failure(s) as per the EASL definitions and/or adapted from CLIF-C Organ Failure (CLIF-C OF)/CLIF- Sequential Organ Failure Assessment (CLIF-SOFA) scores:
1. Respiratory failure or 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;
3. ACLF grade 3: Presence of three or more organ failures as per EASL CLIF criteria as described in the EASL-Clinical Practice Guideline on acute-on-chronic liver failure;
4. Presence of spontaneous or secondary bacterial peritonitis;
5. Presence of spontaneous bacterial pleural empyema;
6. Patients with medical history of spontaneous bacterial peritonitis over the past 2 weeks;
7. Presence of uncontrolled severe infection at SCR or Baseline (BL);
8. Patients with known seizure disorder;
9. Patients with history of upper gastro-intestinal bleeding over the past 7 days, acute bleeding or bleeding upon paracentesis at SCR or BL;
10. Contraindication for paracentesis;
11. Coagulation disorders such as disseminated intravascular coagulation or hemophilia;
12. Transjugular intrahepatic portosystemic shunt procedure or any major abdominal surgery having occurred in the past 4 weeks prior to SCR;
13. Potential or known hypersensitivity to liposomes;
14. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities;
15. Patients after organ transplantation receiving immunosuppressive medication;
16. 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
17. Need for Renal Replacement Therapy or any extracorporeal liver support device (e.g., MARS®, Prometheus®, plasmapheresis);
18. Alfapump® in place to manage ascites;
19. ACLF due to severe alcoholic steatohepatitis in patients with ongoing excessive alcohol intake with a Maddrey Score ≥ 32 requiring steroid treatment;
20. ACLF due to acute viral hepatitis A, B, B+D, C or E requiring antiviral treatment;
21. ACLF due to autoimmune hepatitis requiring high-dose steroid treatment;
22. Pregnancy and lactation;
23. Women of child-bearing potential who are not willing to use adequate contraception;
24. Patients who participate in another clinical trial at the time of SCR or within 4 weeks prior to SCR.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Phase 2a, open-label, randomized, controlled, multicenter, 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 grades 1 and 2 and ascites

Study Details

Disease Type/Condition

Other

Principal Investigator

Kuo, Alexander

Age Group

Adult

Phase

IRB Number

STUDY00002981

ClinicalTrials.gov ID

NCT05900050

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org