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

Ascites Clinical Trial

Official title:

A Phase 2a, Open-label, Randomized, Controlled, Multi-Center Study to Assess the Efficacy, Safety and Tolerability of VS-01 on Top of Standard of Care (SOC), Compared to SOC Alone, in Adult Patients With Acute-on-Chronic Liver Failure (ACLF) Grades 1 and 2 and Ascites

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05900050
• Other study ID #: VS01-IIa-01
• Secondary ID: 2021-002617-33
• Status: Recruiting
• Phase: Phase 2
• Start date: July 2, 2023
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Genfit
• Contact: Versantis AG, Katharina Staufer, MD
• Phone: +333 20 16 40 00
• Email: clinical[@]versantis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

1. Cirrhotic patients diagnosed by standard clinical criteria, imaging findings and/or histology with any underlying etiology;

2. Cirrhotic patients 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 decompensated liver cirrhosis (EASL Clinical Practice Guidelines, 2018);

3. Onset of ACLF not more than 96 h before Screening (SCR);

4. Presence of ascites requiring paracentesis;

5. Patients with body mass index (BMI) < 35 kg/m²;

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 without underlying cirrhosis;

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;

2. Coagulation failure;

3. Severe cardiovascular failure requiring the use of 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 decompensated liver cirrhosis;

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 4 weeks;

7. Known active tuberculosis, or latent tuberculosis requiring treatment;

8. Presence of uncontrolled severe infection at SCR or Baseline (BL);

9. Patients with seizure disorder;

10. Patients with history of upper gastro-intestinal bleeding over the past 2 weeks, acute bleeding or bleeding upon paracentesis at SCR or BL;

11. Contraindication for paracentesis;

12. Coagulation disorders such as disseminated intravascular coagulation, hemophilia, known congenital or acquired Von Willebrand disease or platelet function defects;

13. Transjugular intrahepatic portosystemic shunt procedure or any major abdominal surgery having occurred in the past 4 weeks prior to SCR;

14. Potential or known hypersensitivity to liposomes;

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

16. Patients with known Porto-pulmonary hypertension and hepato-pulmonary syndrome;

17. Patients after organ transplantation receiving immunosuppressive medication;

18. 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, people who inject drugs or individuals formerly injecting drugs on substitution therapy;

19. Need for Renal Replacement Therapy or any extracorporeal liver support device (e.g., MARS®, Prometheus®, Plasmapheresis);

20. Alfapump® in place to manage ascites;

21. ACLF due to severe alcoholic steatohepatitis in patients with ongoing excessive alcohol intake with a Maddrey Score = 32 requiring steroid treatment;

22. ACLF due to acute viral hepatitis A, B, B+D, C or E requiring antiviral treatment;

23. ACLF due to autoimmune hepatitis requiring high-dose steroid treatment;

24. Pregnancy and lactation;

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

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

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• Ascites
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Failure

Intervention

Drug:
• VS-01 on top of SOC
Patients will receive VS-01 intraperitoneally on four consecutive days on top of SOC

Other:
• SOC (Control Group)
Patients will receive SOC for decompensated cirrhosis and ACLF

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Universitair Ziekenhuis Leuven	Leuven	Flemish Brabant
France	Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz	Besançon Cedex	Franche-Comte
France	Hôpital de la Croix Rousse	Lyon
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Jena	Jena	Thüringen
Germany	Universitatsklinikum Munster	Muenster	Nordrhein-Westfalen
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospitali University Of Vall d'Hebron-Vall d'Hebron Research Institute (VHIR)	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Liver Institute at Methodist Dallas	Dallas	Texas
United States	Richmond VA Medical Center	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Versantis AG

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7		7 days
Secondary	Time to death through Days 28 and 90		Day 1 through Days 28 and 90
Secondary	Change in ACLF grade through/at Days 7 and 28		Day 1 through Day 7 and Day 28, at Days 7 and 28
Secondary	28-day and 90-day mortality		At Days 28 and 90
Secondary	Transplant-free survival through/at Days 28 and 90		Day 1 through Days 28 and 90, at Day 28 and 90
Secondary	Incidence rate, severity, and relationship to VS-01 of adverse drug reactions and serious adverse drug reactions.	Safety	Day 0 to Day 90