Phase II Safety Study of 2 Dose Regimens of HepaStem in Patients With ACLF

Study Overview
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Brief Summary
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The study will assess the safety of different dose regimens of HepaStem in cirrhotic Patients with ACLF or with acute decompensation at risk of developing ACLF up to Day 28 of the active study period.

Official Title
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Multicenter Phase II Safety and Preliminary Efficacy Study of 2 Dose Regimens of HepaStem in Patients With Acute on Chronic Liver Failure

Conditions
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Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Biological: HepaStem


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Diagnosed cirrhosis Patient with Acute Decompensation of cirrhosis Serum total Bilirubin ≥ 6 mg/dL (≥100 umol/L) The INR measurement has to be : 1.2 ≤ INR < 2 Main Exclusion Criteria: Absence of portal vein flow Known or medical history of thrombotic events Gastrointestinal hemorrhage requiring blood transfusion Variceal bading or sclerosis within 4 weeks before infusion Septic shock or non-controlled bacterial infection Clinical evidence of aspergilus infection. Circulatory failure Respiratory disordered Coagulation disorders defined as INR ≥ 2, Fibrinogen < 100 mg/dL or Platelets < 50.000/mm3 MELD score > 30. Major invasive procedure within 4 weeks before infusion Previous organ transplantation and/or ongoing immunosuppressive treatments. Renal failure due to chronic kidney disease. Clinically significant left-right cardiac shunt.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low dose cohort<br>Two dose regimens of HepaStem will be given, which differ in the amount of cells per infusion. The low dose regimen will be given to the first cohort (first 6 patients included in the study). | Biological: HepaStem<br> <br> |
| Other: High dose cohort<br>The high dose regimen will be given to the second cohort after evaluation of the safety of the 1st cohort (stepwise approach) | Biological: HepaStem<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by occurence of Adverse Events (AE) up to Day 28 of the active study period |  | up to 28Day post first infusion day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy assessed by clinical parameters | Clinical efficacy parameters evaluated by mortality, liver transplantation and disease scoring. | 28Day, 3 month and 1 year post first infusion day | 
| Efficacy assessed by biological parameters | Biological efficacy parameters evaluated by bilirubin, creatinine, INR and albumin values | 28Day, 3 month and 1 year post first infusion day | 
| Long term safety Follow up assessed by the occurence of Adverse Event of Special Interest | Adverse Event of Special Interest defined as : SAE (Serious Adverse Event) with fatal | 3 month and 1 year post first infusion day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute-On-Chronic Liver Failure, ACLF