Study to Evaluate the Efficacy and Safety of HepaStem in Patients With Acute on Chronic Liver Failure (ACLF)

Study Overview
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Brief Summary
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This is an interventional, double blind, randomized (2:1), and placebo-controlled study of 1 dose regimen of HepaStem in patients recently diagnosed (≤1 week) with ACLF grade 1 or 2 on top of Standard of Care (SoC), and for whom the diagnosis is not resolved on the day of infusion.

Official Title
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Randomized, Placebo-controlled, Double Blind, Multi-centre Phase IIb Study to Evaluate the Efficacy and Safety of HepaStem in Patients With Acute on Chronic Liver Failure (ACLF

Conditions
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Acute on Chronic Liver Failure

Intervention / Treatment
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* Drug: HepaStem
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Initial diagnostic of ACLF, at the investigational site, maximum 3 days before signature of the ICF. Patient with Acute on Chronic Liver Failure Grade 1 or 2 according to the CLIF definition*. Bilirubin value ≥5 mg/dL. Main Exclusion Criteria: ACLF grade 3. Active uncontrolled bleeding or patient with high risk of short term bleeding up to investigator's judgment. Model for End-Stage Liver Disease (MELD) score >35. 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. Mechanical ventilation due to respiratory failure, except for hepatic encephalopathy. Inability to maintain mean BP >60 despite use of vasopressors. Patients receiving immunosuppressive drugs, except glucocorticoids. Thrombosis of portal vein. Underlying cirrhosis due to biliary disease or auto immune hepatitis Coagulation disturbances defined as (Drolz et al. 2016; Nadim et al. 2016): fibrinogen <80 mg/dL platelets <50 x 10³/mm3

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HepaStem<br>Patients in the HepaStem arm will receive 2 infusions of HepaStem (i.v) at 1.0 millions of cells/kg (7 day interval) | Drug: HepaStem<br>* HepaStem will be administered as an intravenous (IV) infusion<br>|
| Placebo Comparator: Placebo<br>Patients in the placebo arm will receive 2 infusions of placebo (i.v) (7 day interval) | Drug: Placebo<br>* Placebo will be administered as an intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival proportion 90 days post-first infusion. | Overall Survival proportion | 90 days post first infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant-free survival proportion 90 days post-first infusion. | Liver Transplant-free survival proportion | 90 days post first infusion | 
| Liver function parameters up to 1-year post-infusion | CLIF-C ACLF score | up to 1-year post first infusion. | 
| Liver function parameters up to 1-year post-infusion | MELD score | up to 1-year post first infusion. |