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.
- Conditions
- Cirrhotic patients who are hospitalized for Acute on chronic liver failure (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 28days). The development of ACLF is associated with exacerbated systemic inflammation that may indeed cause organ failures.Therapeutic area: Diseases [C] - Digestive System Diseases [C06]MedDRA version: 24.0Level: PTClassification code 10077305Term: Acute on chronic liver failureSystem Organ Class: 10019805 - Hepatobiliary disorders
- Registration Number
- EUCTR2019-003051-11-BG
- Lead Sponsor
- Promethera Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 100
Patients must fulfill all of the following criteria in order to be eligible for
trial enrollment:
1. Are adults aged between 18 and 70 years old.
2. Have an initial diagnosis of ACLF at the investigational site.
3. Have ACLF grade 1 or 2 according to the EASL-CLIF Consortium
definition.
4. Have a total bilirubin = 5 mg/dL.
5. Are able to read, understand and give written informed consent.
If the patient is unable to fully understand the study and based on the
investigator's judgment, the ICF must be signed by a legal or authorized
representative of the patient according to local regulation. In case of
hepatic encephalopathy (HE), the ICF must be signed by the patient after
encephalopathy improvement, if possible.
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) yes
F.1.3.1 Number of subjects for this age range 30
Patients presenting with any of the following criteria will not be included
in the study:
1. Have a MELD-Na score > 35.
2. Have underlying cirrhosis due to biliary disease.
3. Have underlying cirrhosis due to autoimmune hepatitis.
4. Have active bleeding at a non-compressible site or at a compressible
site that, in the opinion of the investigator, poses an unacceptable risk
for the patient's participation in the study.
5. Have received treatment for bleeding complications during the current
hospitalization and has a persistent high risk for re-bleeding that, in the
opinion of the investigator, poses an unacceptable risk for the patient's
participation in the study.
6. Have a complete portal vein thrombosis.
7. Have coagulation disturbances defined as:
o fibrinogen < 80 mg/dL
o platelets < 50 x 10³/mm³
8. Are requiring chronic dialysis therapy.
9. Have had a 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.
10. Have a previous history of myocardial infarction and/or cardiac
failure, with an ejection fraction rate (EFR) = 40%.
11. Have an inability to maintain mean blood pressure (BP) > 60 mmHg
despite use of vasopressors.
12. Have severe pulmonary arterial hypertension defined as mean
pulmonary arterial pressure (MPAP) = 45 mmHg (or right ventricular
systolic pressure = 50 mmHg) by echocardiography.
13. Have hepatopulmonary syndrome.
14. Are receiving mechanical ventilation due to respiratory failure.
15. Have known or suspected hypersensitivity or allergy to any of the
components of the HepaStem diluent, dimethyl sulfoxide (DMSO), or
bovine serum albumin.
16. Have a history of severe allergies to drugs and/or a history of severe
anaphylactic reactions.
17. Have undergone a major invasive procedure within 2 weeks of
randomization. These are open surgeries (the proper healing of the scar
should be verified by the investigator).
o Liver biopsy (transjugular or percutaneous), paracentesis, and
transjugular intrahepatic portosystemic shunt (TIPS) are not considered
as major invasive procedures.
18. Had a previous organ transplantation and/or treatment with cellbased
therapy.
19. Are accepted as High Urgency status patient by the organ allocation
system.
20. Have active primary or recurrent malignant disease (including
hepatocellular carcinoma) or have been in remission from clinically significant malignancy for < 5 years.
o Patients with cervical carcinoma in situ that has been resected with no
evidence of recurrence or metastatic disease for at least 3 years may
participate in the study.
o Patients with basal cell or squamous epithelial skin cancers that have
been completely resected with no evidence of recurrence for at least 3
years may participate in the study.
21. Are receiving immunosuppressive drugs, except glucocorticoids.
o Patients receiving glucocorticoids administered for treatment of severe
alcoholic hepatitis may participate in the study.
22. Have a contraindication to or are unwilling to take glucocorticoids to
prevent infusion-like reaction.
23. Have persistently positive blood cultures despite 48 hours of
antibiotic therapy that indicates uncontrolled bacterial infection.
24. Have diagnosis of invasive aspergillosis.
25. Have known infection with human immunodeficiency virus (HIV).
26. Have a history of hepatitis D virus infection.
27. Are women of childb
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