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

Primary Purpose

Acute-On-Chronic Liver Failure, Ascites

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
VS-01 on top of SOC
SOC (Control Group)
Sponsored by
Versantis AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute-On-Chronic Liver Failure focused on measuring Chronic liver diseases, Hepatic Dysfunction, Extrahepatic Organ Dysfunction, Liver Failure, Renal Disease, Hepatic Impairment, Renal Impairment, Hepatic Decompensation, Cirrhosis

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Universitatsklinikum MunsterRecruiting
  • Universitätsklinikum JenaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

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

SOC (Control Group)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7

Secondary Outcome Measures

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

Full Information

First Posted
June 2, 2023
Last Updated
July 19, 2023
Sponsor
Versantis AG
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1. Study Identification

Unique Protocol Identification Number
NCT05900050
Brief Title
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 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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 2, 2023 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Versantis AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VS-01 on top of SOC (Active Treatment Group)
Arm Type
Experimental
Arm Description
Patients randomized to Active Treatment group will receive VS-01 on top of SOC
Arm Title
SOC (Control Group)
Arm Type
Other
Arm Description
Patients randomized to Control group will receive SOC defined as the standard medical management of patients with decompensated cirrhosis and ACLF
Intervention Type
Drug
Intervention Name(s)
VS-01 on top of SOC
Intervention Description
Patients will receive VS-01 intraperitoneally on four consecutive days on top of SOC
Intervention Type
Other
Intervention Name(s)
SOC (Control Group)
Intervention Description
Patients will receive SOC for decompensated cirrhosis and ACLF
Primary Outcome Measure Information:
Title
Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Time to death through Days 28 and 90
Time Frame
Day 1 through Days 28 and 90
Title
Change in ACLF grade through/at Days 7 and 28
Time Frame
Day 1 through Day 7 and Day 28, at Days 7 and 28
Title
28-day and 90-day mortality
Time Frame
At Days 28 and 90
Title
Transplant-free survival through/at Days 28 and 90
Time Frame
Day 1 through Days 28 and 90, at Day 28 and 90
Title
Incidence rate, severity, and relationship to VS-01 of adverse drug reactions and serious adverse drug reactions.
Description
Safety
Time Frame
Day 0 to Day 90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Versantis AG, Katharina Staufer, MD
Phone
+41 76 469 88 96
Email
clinical@versantis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Carol Addy, MD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katharina Staufer, MD
Organizational Affiliation
Versantis AG
Official's Role
Study Director
Facility Information:
Facility Name
Universitatsklinikum Munster
City
Muenster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Jena
City
Jena
State/Province
Thüringen
ZIP/Postal Code
07747
Country
Germany
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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