A clinical study to evaluate a new medicinal product VS-01 in patients with an acute episode on top of a chronic liver disease (called acute-on-chronic liver failure) who experience accumulation of fluid in the abdominal cavity (called ascites) as well as intellectual, behavioral decay and physical decay.

Phase 1

Active, not recruiting

• Conditions: Acute-on-chronic liver failure (ACLF) is characterized by hepatic and extrahepatic organ dysfunction and/or failure and highly activated systemic inflammation. It leads to an accumulation of different metabolites, interalias ammonia, which cannot be metabolized. Hyperammonemia leads to Hepatic Encephalopathy (HE). ACLF is a major cause of death in cirrhosis, with an approximately 50% mortality rate. The selected patient population is ACLF grade 1 and 2 patients with ascites.; MedDRA version: 24.0Level: PTClassification code 10077305Term: Acute on chronic liver failureSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2021-002617-33-ES
• Lead Sponsor: Versantis AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-18
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 70

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 to 2 (according to EASL-CLIF criteria as described in the EASL-Clinical Practice Guideline on decompensated liver cirrhosis (EASL Clinical Practice Guidelines, 2018); organ failures will be calculated based on the CLIF-C OF score) triggered by any acute insult other than those listed in the exclusion criteria:
ACLF Grade 1 patients meeting one of the following:
a. Kidney failure (serum creatinine = 2 mg/dL without renal replacement therapy [RRT]) + HE West Haven Grade 2;
b. Liver failure (serum bilirubin = 12.0 mg/dL) + HE West Haven Grade 2 with or without kidney dysfunction (serum creatinine = 1.5 – < 2.0 mg/dL);
c. Corrected Coagulation failure (International Normalized Ratio [INR] = 2.5), i.e., not requiring continuous transfusion + HE West Haven Grade 2 with or without kidney dysfunction (serum creatinine = 1.5 - < 2.0 mg/dL);
d. HE West Haven Grade 3 + kidney dysfunction (serum creatinine = 1.5 - < 2.0 mg/dL).
ACLF Grade 2 patients meeting one of the following:
e. Kidney failure (serum creatinine = 2 mg/dL without RRT) + HE West Haven Grade 3;
f. Liver failure (serum bilirubin = 12.0 mg/dL) + HE West Haven Grade 3;
g. Corrected Coagulation failure (INR = 2.5), i.e., not requiring continuous transfusion + HE West Haven Grade 3.
3. Same ACLF Grade 1 or 2, for at least 24 h of hospitalization before Screening;
4. Diagnosis of ACLF not more than 96 h before Screening;
5. Presence of ascites with clinical decision for paracentesis;
6. Fasting venous ammonia plasma levels above the upper limit of normal;
7. Patients with body mass index (BMI) < 35 (calculated on dry weight);
8. Men and women = 18 and = 64 years of age on the day of signing Patient Informed Consent Document (PICD);
9. Informed consent:
a. Ability to understand the PICD and comply with the protocol and sign the PICD or a legal representative can sign PICD. If patients are temporarily unable to consent and are considered in an emergency situation, they will be included according to local law and Ethics Committees (EC) requirements and need to consent as soon as they are able again to do so;
b. Signed and dated PICD obtained prior to performing any study procedure, including Screening, except for patients who are considered in an emergency situation and for whom the PICD will be obtained as soon as it is possible and reasonable by the patient themselves or by a legal representative who can sign the PICD on behalf of the patient.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Presence of the following organ(s) failure(s) as per the EASL (EASL Clinical Practice Guidelines, 2018) definitions and CLIF-C OF score:
a. Respiratory failure as defined by PaO2/ FiO2 = 200, or SpO2/ FiO2 = 214 or mechanical ventilation;
b. Uncorrected coagulation failure as defined by INR (INR = 2.5 or platelet count = 20 x 109/L);
c. Severe cardiovascular failure requiring the use of vasopressors. It should be clarified that the use of terlipressin or low-dose norepinephrine in case of hepatorenal syndrome (HRS) or bleeding is not an exclusion criterion;
2. 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 ((EASL Clinical Practice Guidelines, 2018); organ failures will be calculated based on CLIF-C OF score);
3. Presence of uncontrolled and severe infection at Screening:
a. Criteria for diagnosis of infections will be the presence of clinical signs of infection according to criteria adapted from the EASL Clinical Practice Guidelines 2018 (EASL Clinical Practice Guidelines, 2018) for the management of patients with decompensated cirrhosis:
i.Any spontaneous or secondary bacterial peritonitis: presence of neutrophils in a normally sterile body fluid (e.g., neutrophil counts > 250/mm3 ascitic fluid);
ii.Any spontaneous bacterial pleural empyema: In case of pleural effusion, positive pleural fluid culture and increased neutrophil count of > 250/mm3 or negative pleural fluid culture and a neutrophil count of > 500/mm3 in the absence of pneumonia;
b. UTIs with hemodynamic instability or septic shock;
c. Pneumonia with hemodynamic instability or septic shock;
d. Documented or active tuberculosis;
e. Skin/soft tissue infection: physical examination findings of swelling, erythema, heat and tenderness in the skin with hemodynamic instability or septic shock;
f. Acute obstructive cholangitis in the presence of cholestasis, compatible symptoms (right upper quadrant pain and jaundice) and radiological data of biliary obstruction with hemodynamic instability or septic shock;
g. Patients with colonized (> 2 sites) or invasive fungal infection;
h. Patients with sepsis or septic shock of unknown source;
4. Patients with medical history of spontaneous bacterial peritonitis over the past 4 weeks;
5. Patients with epilepsy;
6. Presence of on-going gastro-intestinal bleeding or bleeding upon paracentesis at Screening;
7. Contraindication for paracentesis according to the EASL Clinical Practice Guidelines 2018 (EASL Clinical Practice Guidelines, 2018) for the management of patients with decompensated cirrhosis;
8. Other known coagulation disorders such as hemophilia, congenital or acquired Von Willebrand disease or platelets function defects;
9. For any of the following having occurred in the past 4 weeks prior to screening: TIPS procedure, banding of an esophageal varix or any major abdominal surgery;
10. Potential or known hypersensitivity to liposomes;
11. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase), increased complement activation; previous reactions to medicinal products; multiple hypersensitivities;
12. Patients with known PPHT and hepato-pulmonary syndrome;
13. Any transplanted patients receiving immunosuppressant medication;
14. Any severe disease considered to be potentially detrimental at the discretion of the PI. T

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified