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

Versantis

Status and phase: Enrolling; Phase 2

Conditions: Acute-On-Chronic Liver Failure; Ascites

Treatments: Other: SOC (Control Group); Drug: VS-01 on top of SOC

Study type: Interventional

Funder types: Industry

Identifiers

NCT05900050

2024-513706-56-00 (EU Trial (CTIS) Number)

VS01-IIa-01

Details and patient eligibility

About

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)

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

VS-01 on top of SOC (Active Treatment Group)

Experimental group

Description:

Patients randomized to Active Treatment group will receive VS-01 on top of SOC

Treatment:

Drug: VS-01 on top of SOC

SOC (Control Group)

Other group

Description:

Patients randomized to Control group will receive SOC defined as the standard medical management of patients with decompensated cirrhosis and ACLF

Treatment:

Other: SOC (Control Group)