This trial will evaluate the safety and efficacy of HepaStem compared toplacebo in patients with a cirrhotic liver condition called Acute on ChronicLiver Failure (ACLF). The study will be performed in multiple centers and ina double-blinded manner, meaning neither the patients nor the treatingphysicians know who is on placebo or the study drug.

Phase 1

• Conditions: Cirrhotic patients who are hospitalized for Acute on chronic liver failure(ACLF), ACLF combines an acute deterioration of liver function in anindividual with pre-existing chronic liver disease and extrahepatic organfailures 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: EUCTR2019-003051-11-GB
• Lead Sponsor: Promethera Biosciences

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-19
• Last Update Posted: 13 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 363

Inclusion Criteria

Patients must fulfil all of the following criteria in order to be eligible for
trial enrolment:
1. Adult aged 18 years and above.
2. Initial diagnostic of ACLF, at the investigational site, maximum 3 days
before signature of the ICF.
3. Patient with Acute on Chronic Liver Failure Grade 1 or 2 according to the CLIF definition*.
4. Bilirubin value = 5 mg/dL.
5. 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 a patient's legal or authorized
representative according to local regulation, and by the patient, if
possible, after encephalopathy improvement.
* ACLF grading is based on the number of organ failure as defined per
the CLIF-OF score (Arroyo et al. 2015);
http://www.efclif.com/scientific-activity/score-calculators/clif-c-aclf

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 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 73

Exclusion Criteria

Patients presenting with any of the following will not be included in the
study:
1. ACLF grade 3.
2. Active uncontrolled bleeding or patient with high risk of short term
bleeding up to investigator's judgment.
3. Model for End-Stage Liver Disease (MELD) score > 35.
4. Cerebrovascular, myocardial, limb arterial thrombotic event, or history
for both thrombotic and hemorrhagic cerebrovascular events within 12
months prior to the screening and not considered stabilized by the
investigator.
5. Mechanical ventilation due to respiratory failure, except for hepatic
encephalopathy.
6. Inability to maintain mean BP > 60 despite use of vasopressors.
7. Patients receiving immunosuppressive drugs, except glucocorticoids.
8. Thrombosis of portal vein.
9. Underlying cirrhosis due to biliary disease (primary sclerosing
cholangitis, primary biliary cholangitis…).
10. Underlying cirrhosis due to autoimmune hepatitis.
11. Coagulation disturbances defined as (Drolz et al. 2016; Nadim et al.
2016):
a. fibrinogen < 80 mg/dL
b. platelets < 50 x 10³/mm³
12. Uncontrolled bacterial infection upon judgment of the investigator.
13. Proven or probable invasive aspergillosis (Gustot et al. 2014).
14. Major invasive procedure within 2 weeks before the infusion. These
are open surgeries (the proper healing of the scar should be verified by
the investigator). N.B.: Liver biopsy (trans jugular or percutaneous),
paracentesis, TIPS are not considered as a major invasive procedure.
15. Previous organ transplantation and/or treatment with cells.
16. Previous hepatectomy.
17. Severe pulmonary arterial hypertension defined as mean pulmonary arterial pressure (MPAP) =45 mmHg.
18. Hepatopulmonary syndrome.
19. Known or suspected hypersensitivity or allergy to any of the
components of the HepaStem Diluent (human albumin, heparin sodium
and sodium bicarbonate, DMSO), bovine serum, or a history of multiple
and/or severe allergies to drugs or foods or a history of severe
anaphylactic reactions.
20. Patients with active cancer or history of cancer unless adequately
treated and/or in complete remission for five or more years.
21. Hepatocellular carcinoma.
22. On haemodialysis due to chronic kidney disease.
23. Known infection with human immunodeficiency virus (HIV).
24. Pregnancy (negative ß-HCG test required) and nursing women, or
women with childbearing potential who decline to use highly effective
contraception methods during the study. Authorized methods of
contraception are listed in Section 10.14.2.
25. Participation in any other interventional study within the last 4
weeks, or participation and/or under follow-up in another clinical trial.
26. 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.
27. Patients who are employees of the Sponsor or investigator, or
otherwise dependent on them; Patients committed to an institution by
virtue of an order issued either by the judicial or the administrative
authorities
28. Accepted as High Urgency status patient by the organ allocation
system (ex: Eurotransplant or equivalent)
Depending on the reason of screening failures, a patient could be
retested again (Visit 1 re-test) after consultation with the sponsor.

Study & Design

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