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

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Acute-On-Chronic Liver Failure, Ascites

Intervention / Treatment
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* Drug: VS-01 on top of SOC
* Other: SOC (Control Group)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhotic patients diagnosed by standard clinical criteria, imaging findings and/or histology with any underlying etiology; 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); Onset of ACLF not more than 96 h before Screening (SCR); Presence of ascites requiring paracentesis; Patients with body mass index (BMI) < 35 kg/m²; Written informed consent obtained prior to the start of any study-related procedures. Exclusion Criteria: Patients with acute or sub-acute liver failure without underlying cirrhosis; 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: Respiratory failure; Coagulation failure; Severe cardiovascular failure requiring the use of vasopressors; 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; Presence of spontaneous or secondary bacterial peritonitis; Presence of spontaneous bacterial pleural empyema; Patients with medical history of spontaneous bacterial peritonitis over the past 4 weeks; Known active tuberculosis, or latent tuberculosis requiring treatment; Presence of uncontrolled severe infection at SCR or Baseline (BL); Patients with seizure disorder; Patients with history of upper gastro-intestinal bleeding over the past 2 weeks, acute bleeding or bleeding upon paracentesis at SCR or BL; Contraindication for paracentesis; Coagulation disorders such as disseminated intravascular coagulation, hemophilia, known congenital or acquired Von Willebrand disease or platelet function defects; Transjugular intrahepatic portosystemic shunt procedure or any major abdominal surgery having occurred in the past 4 weeks prior to SCR; Potential or known hypersensitivity to liposomes; Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities; Patients with known Porto-pulmonary hypertension and hepato-pulmonary syndrome; Patients after organ transplantation receiving immunosuppressive medication; 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; Need for Renal Replacement Therapy or any extracorporeal liver support device (e.g., MARS®, Prometheus®, Plasmapheresis); Alfapump® in place to manage ascites; ACLF due to severe alcoholic steatohepatitis in patients with ongoing excessive alcohol intake with a Maddrey Score ≥ 32 requiring steroid treatment; ACLF due to acute viral hepatitis A, B, B+D, C or E requiring antiviral treatment; ACLF due to autoimmune hepatitis requiring high-dose steroid treatment; Pregnancy and lactation; Women of child-bearing potential who are not willing to use adequate contraception; Patients who participate in another clinical trial at the time of SCR or within 4 weeks prior to SCR.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VS-01 on top of SOC (Active Treatment Group)<br>Patients randomized to Active Treatment group will receive VS-01 on top of SOC | Drug: VS-01 on top of SOC<br>* Patients will receive VS-01 intraperitoneally on four consecutive days on top of SOC<br>|
| Other: SOC (Control Group)<br>Patients randomized to Control group will receive SOC defined as the standard medical management of patients with decompensated cirrhosis and ACLF | Other: SOC (Control Group)<br>* Patients will receive SOC for decompensated cirrhosis and ACLF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7 |  | 7 days | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic liver diseases, Hepatic Dysfunction, Extrahepatic Organ Dysfunction, Liver Failure, Renal Disease, Hepatic Impairment, Renal Impairment, Hepatic Decompensation, Cirrhosis