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-ES

Lead Sponsor: Promethera Biosciences

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

1. Adult aged between 18 and 70 year old.
2. Signed Informed Consent.
N.B: In case of hepatic encephalopathy, if the patient is not able to fully 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)
6. The INR measurement has to be : 1.2 = INR < 2
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Absence of portal vein flow as assessed by Doppler ultrasound or other exam.
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. Gastrointestinal hemorrhage requiring blood transfusion unless controlled for more than 4 weeks prior to the first infusion.
4. Variceal banding or sclerosis within 4 weeks before the infusion.
5. Septic shock or non-controlled bacterial infection defined as persistent clinical signs of infection despite adequate antibiotic therapy for more than 48h.
6. Clinical evidence of Aspergillus infection.
7. Circulatory failure defined as treated with vasoconstrictors to maintain arterial pressure or inotropes to improve cardiac output. N.B:
Use of terlipressin to control increased levels of creatinine is not an exclusion criterion.
8. Respiratory disorders with pulse oximetry < 93% and related clinical signs, requiring or not mechanical ventilation.
9. Coagulation disorders defined as :
• INR = 2
• Fibrinogen < 100 mg/dL
• Platelets < 50.000/mm3
10. Major invasive procedure within 4 weeks before the infusion (within 1 week for minor invasive procedure such as e.g. transjugular liver biopsy). The proper healing of the puncture site should be verified by the investigator.
11. Treatment with corticosteroids for acute liver disease less than 1 day before the start of the screening period.
12. MELD score > 30.
13. Previous organ transplantation and/or ongoing immunosuppressive treatments.
14. Postoperative-decompensation following hepatectomy.
15. Renal failure due to chronic kidney disease.
16. Clinically significant left-right cardiac shunt.
17. 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.
18. Malignancies, other than curatively treated skin cancer, unless a complete remission over 5 years.
19. Refusal of abstinence from alcohol for at least 5 weeks from the study enrolment.
20. Pregnancy (negative ß-HCG test required) or women with childbearing potential who decline to use reliable contraceptive methods
during the study.
21. Participation to any other interventional study within the last 4 weeks.
22. 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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