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

Phase 2

Recruiting

• Conditions: Ascites; Acute-On-Chronic Liver Failure
• Interventions: Drug: VS-01 on top of SOC; Other: SOC (Control Group)

• Registration Number: NCT05900050
• Lead Sponsor: Versantis AG

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-02
• Study First Submitted QC: 2023-06-02
• Study First Posted: 2023-06-12
• Study Start: 2023-07-02
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-14
• Primary Completion: 2025-10
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VS-01 on top of SOC (Active Treatment Group)	VS-01 on top of SOC	Patients randomized to Active Treatment group will receive VS-01 on top of SOC
SOC (Control Group)	SOC (Control Group)	Patients randomized to Control group will receive SOC defined as the standard medical management of patients with decompensated cirrhosis and ACLF

Primary Outcome Measures

Name	Time	Method
Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7	7 days

Secondary Outcome Measures

Name	Time	Method
Transplant-free survival through/at Days 28 and 90	Day 1 through Days 28 and 90, at Day 28 and 90
Time to death through Days 28 and 90	Day 1 through Days 28 and 90
28-day and 90-day mortality	At Days 28 and 90
Incidence rate, severity, and relationship to VS-01 of adverse drug reactions and serious adverse drug reactions.	Day 0 to Day 90	Safety
Change in ACLF grade through/at Days 7 and 28	Day 1 through Day 7 and Day 28, at Days 7 and 28

Trial Locations

Locations (30)

Centre Hospitalier Régional Universitaire de Tours; 🇫🇷 Chambray-lès-Tours, France

Hôpital de la Croix Rousse; 🇫🇷 Lyon, France

CHU Rennes - Hôpital Pontchaillou; 🇫🇷 Rennes, France

Universitatsklinikum Munster; 🇩🇪 Muenster, Nordrhein-Westfalen, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Thüringen, Germany

Charité Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Hospital University Of Vall d'Hebron-Vall d'Hebron Research Institute (VHIR); 🇪🇸 Barcelona, Spain

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro- Majadahonda; 🇪🇸 Madrid, Spain

Hospital Universitari y Politècnic La Fe; 🇪🇸 Valencia, Spain

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

Piedmont Atlanta Hospital; 🇺🇸 Atlanta, Georgia, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Missouri Health Care; 🇺🇸 Columbia, Missouri, United States

Columbia University Medical Center/ New York Presbyterian Hospital; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

The Liver Institute at Methodist Dallas; 🇺🇸 Dallas, Texas, United States

Baylor Clinic; 🇺🇸 Houston, Texas, United States

Richmond VA Medical Center; 🇺🇸 Richmond, Virginia, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Universitair Ziekenhuis Leuven; 🇧🇪 Leuven, Flemish Brabant, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Oost-Vlaanderen, Belgium

Universitair Ziekenhuis Antwerpen; 🇧🇪 Edegem, Belgium

Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz; 🇫🇷 Besançon Cedex, Franche-Comte, France