The study will study the safety and preliminary efficacy of HepaStem in cirrhotic patients who are hospitalized for Acute on Chronic Liver Failure (ACLF) or acute decompensation at risk of developing ACLF.The study is divided in 4 periods: screening period, active study period divided in treatment period and evaluation period, and long-term safety follow-up.

Phase 1

Conditions: The study will recruit cirrhotic patients who are hospitalized for Acute-on-chronic liver failure (ACLF) or Acute Decompensation at risk of developing ACLF. ACLF combines an acute deterioration of liver function in an individual with pre-existing chronic liver disease and extrahepatic organ failures characterized by high short-term mortality (30-40% at 28 days). The development of ACLF is associated with exacerbated systemic inflammation that may indeed cause organ failures.
MedDRA version: 20.0Level: LLTClassification code 10008954Term: Chronic liver disease and cirrhosisSystem Organ Class: 100000004871
MedDRA version: 20.1Level: LLTClassification code 10049844Term: Acute liver failureSystem Organ Class: 100000004871
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2016-001177-32-BE

Lead Sponsor: Promethera Biosciences

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 21

Inclusion Criteria

A patient must fulfill all of the following criteria to be eligible to participate in the study:
1. Adult aged between 18 and 70 years old.
2. Informed Consent.
N.B: In case of hepatic encephalopathy, if the patient is not able to understand the study based on the investigator’s judgment, the Informed Consent must be signed by patient’s legal representative according to local regulation, and by the patient, if possible, after encephalopathy improvement.
3. Cirrhosis as diagnosed by (1) liver histology or (2) by clinical and imaging examination (may include fibroscan).
4. Patient with Acute Decompensation of cirrhosis
5. Serum total Bilirubin = 6 mg/dL (=100 umol/L)
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 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

Any of the following criteria will exclude a patient from the study:
1. Thrombosis of the portal vein.
2. Recurrent or ongoing thrombotic events or patients considered with high risk of thrombosis at the time of infusion.
Any thrombosis history should be discussed with the medical monitor before exclusion / inclusion in the study, in a case by case discussion.
3. Ongoing uncontrolled bleeding.
4. Septic shock or non-controlled bacterial infection defined as persistent clinical signs of infection despite adequate antibiotic therapy for more than 48h.
5. Clinical evidence of Aspergillus infection.
6. Circulatory failure defined by inability to maintain a mean blood pressure =70 despite use of vasopressors.
7. Mechanical ventilation due to respiratory failure.
8. Coagulation disorders defined as:
• Fibrinogen < 80 mg/dL
• Platelets < 40.000/mm3
9. Major invasive procedure within 4 weeks before the infusion (within 1week for minor invasive procedure such as e.g. transjugular liver biopsy). The proper healing of the puncture site should be verified by the investigator.
10. Treatment with corticosteroids for acute liver disease less than 1 day before the start of the screening period.
11. MELD score > 35.
12. Previous organ transplantation and/or ongoing immunosuppressive treatments.
13. Postoperative-decompensation following hepatectomy.
14. Renal failure due to chronic kidney disease.
15. Clinically significant left-right cardiac shunt.
16. Known or suspected hypersensitivity or allergy to any of the components of the HepaStem Diluent (human albumin, heparin sodium and sodium bicarbonate) or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.
17. Malignancies, other than curatively treated skin cancer, unless a complete remission over 5 years. In case of suspicion of HCC, all exam should be done to confirm or not the diagnosis prior enrolment.
18. Refusal of abstinence from alcohol for at least 5 weeks from the study enrolment.
19. Pregnancy (negative ß-HCG test required) or women with childbearing potential who decline to use reliable contraceptive methods during the study.
20. Participation to any other interventional study within the last 4 weeks.
21. Any significant medical or social condition or disability that, in the Investigator’s opinion, may warrant a specific treatment, or may interfere with the patient’s optimal participation or compliance with the study procedures.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials