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: Cirrhotic patients who are hospitalized for Acute on-chronic liver failure (ACLF) or Acute Decompensation at risk ofdeveloping ACLF. ACLF combines an acute deterioration of liver functionin an individual with pre-existing chronic liver disease and extrahepaticorgan failures characterized by high short-term mortality (30-40% at 28days). The development of ACLF is associated with exacerbated systemicinflammation 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-BG

Lead Sponsor: Promethera Biosciences

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 21

Inclusion Criteria

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) no
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

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

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