Acute-On-Chronic Liver Failure, Ascites
Conditions
Keywords
Chronic liver diseases, Hepatic Dysfunction, Extrahepatic Organ Dysfunction, Liver Failure, Renal Disease, Hepatic Impairment, Renal Impairment, Hepatic Decompensation, Cirrhosis
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)
Interventions
DRUGVS-01 on top of SOC
Patients will receive VS-01 intraperitoneally on four consecutive days on top of SOC
OTHERSOC (Control Group)
Patients will receive SOC for decompensated cirrhosis and ACLF
Sponsors
Genfit
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chronic Liver Failure Consortium (CLIF-C) ACLF Score at Day 7 | Day 7 | The CLIF-C ACLF score is derived from the CLIF-C organ failure (OF) score. The formula for the CLIF-C ACLF score is CLIF-ACLF = 10\*\[0.33\*CLIF-C OF + 0.04\*Age + 0.63\*Ln(white cell count) -2\]. The CLIF-C ACLF score ranges from 0-100, where a higher score indicated a greater mortality risk. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Deaths From Day 1 to Day 90 | Day 1 to Day 90 | 90-Day mortality was reported as the number of deaths from Day 1 to Day 90. |
| Number of Deaths From Day 1 to Day 28 | Day 1 to Day 28 | 28-Day mortality was reported as the number of deaths from Day 1 to Day 28. |
| Time to Death Through Day 90 | Day 1 to Day 90 | Time to death was calculated as death date - treatment start date. Participants who were not observed to have encountered the event through Day 90 were censored. The inter-quartile range was obtained via Kaplan Meier estimation. |
| Number of Participants With ACLF Resolution | Baseline to Day 7 and Day 28 | ACLF resolution was defined as ACLF grade 'No ACLF', for participants who had ACLF at Baseline. |
| Time to ACLF Resolution Through Day 28 | Baseline to Day 28 | ACLF resolution was defined as ACLF grade 'No ACLF', for participants who had ACLF at Baseline. Time to ACLF resolution was calculated as (ACLF resolution date - treatment start date). Participants who were not observed to have encountered the event through Day 28 were censored at min\[trial discontinuation date; Day 28 visit date or treatment start date +27 if no visit date; last contact/assessment date for participant lost to follow-up; date of liver transplant or transjugular intrahepatic portosystemic shunt (TIPS)\]. The inter-quartile range was obtained via Kaplan Meier estimation. |
| Number of Participants With ≥ 1 ACLF Grade Regression | Baseline, Day 7 and Day 28 | ACLF regression was defined as regression of at least one full grade. |
| Time to ≥ 1 ACLF Grade Regression Through Day 28 | Baseline and Day 28 | Time to ACLF ≥ 1 grade regression was calculated as (ACLF ≥ 1 grade regression date - treatment start date). Participants who were not observed to have encountered the event through Day 28 were censored. The inter-quartile range was obtained via Kaplan Meier estimation. |
| Secondary: Time to Transplant or Death Through Day 90 | Day 1 through Day 90 | Time to transplant was calculated as (transplant or death date - treatment start date). Participants who were not observed to have encountered the event through Day 90 were censored. The inter-quartile range was obtained via Kaplan Meier estimation. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 90 | An AE was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a study drug and that does not necessarily have a causal relationship with this treatment. A TEAE was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after at least one dose of the study drug had been administered, even if the event was not considered to be related to the study drug. A serious AE (SAE) was any untoward medical event that occurs at any dose that: resulted in death; was life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; or was an important medical event. |
Countries
Belgium, France, Germany, Hungary, Italy, Spain, United States
Contacts
STUDY_DIRECTORPejvack MOTLAGH, M.D, M.Sc
Genfit
Participant flow
Recruitment details
A total of 15 participants were enrolled into this trial in the United States, Germany and France between July 2023 and October 2025.
Pre-assignment details
The total duration of the trial for each participant was up to 94 days. The screening period was up to 4 days, and participants were followed from Day 1 up to Day 90. The trial was discontinued prematurely at the Sponsor's decision.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54.43 years STANDARD_DEVIATION 9.571 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 9 | 2 / 6 |
| other Total, other adverse events | 9 / 9 | 6 / 6 |
| serious Total, serious adverse events | 7 / 9 | 5 / 6 |
Outcome results
None listed