Clinical trial NCT05900050: Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)®
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute-On-Chronic Liver Failure
Ascites
Keywords: Chronic liver diseases
Hepatic Dysfunction
Extrahepatic Organ Dysfunction
Liver Failure
Renal Disease
Hepatic Impairment
Renal Impairment
Hepatic Decompensation
Cirrhosis
Lead sponsor: Genfit
Sponsor class: INDUSTRY
First posted: 2023-06-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7
timeFrame: 7 days
Secondary outcomes:
measure: Time to death through Days 28 and 90
timeFrame: Day 1 through Days 28 and 90
measure: Change in ACLF grade through/at Days 7 and 28
timeFrame: Day 1 through Day 7 and Day 28, at Days 7 and 28
measure: 28-day and 90-day mortality
timeFrame: At Days 28 and 90
measure: Transplant-free survival through/at Days 28 and 90
timeFrame: Day 1 through Days 28 and 90, at Day 28 and 90
measure: Incidence rate, severity, and relationship to VS-01 of adverse drug reactions and serious adverse drug reactions.
timeFrame: Day 0 to Day 90
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center/ New York Presbyterian Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas
state: Texas
city: Houston
country: United States
facility: Baylor Clinic
state: Texas
city: Richmond
country: United States
facility: Richmond VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Flemish Brabant
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Besançon Cedex
country: France
facility: Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz
state: Franche-Comte
city: Chambray-lès-Tours
country: France
facility: Centre Hospitalier Régional Universitaire de Tours
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Rennes
country: France
facility: CHU Rennes - Hôpital Pontchaillou
city: Muenster
country: Germany
facility: Universitatsklinikum Munster
state: Nordrhein-Westfalen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Barcelona
country: Spain
facility: Hospital University Of Vall d'Hebron-Vall d'Hebron Research Institute (VHIR)
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro- Majadahonda
city: Valencia
country: Spain
facility: Hospital Universitari y Politècnic La Fe
Study officials:
affiliation: Versantis AG
name: Katharina Staufer, MD
role: STUDY_DIRECTOR
References: