HEP201-PANASH is an interventional study of increasing doses of HepaStem for the treatment of patients with cirrhotic and pre-cirrhotic NASH. The population will be divided in 4 cohorts and a total of 2 doses are planned to be administered as single or repeated infusions in an ascending manner. The safety and tolerability of HepaStem in the treatment of NASH will be first evaluated as well as preliminary efficacy.

Phase 1

• Conditions: ASH is characterized by steatosis, inflammation and cytological ballooning with varying amounts of fibrosis. Patients with NASH are at risk of cardiovascular morbidity and mortality. In chronic liver disease, changes in inflammatory components of the liver are not limited to the sole organ, but has a systemic influence. Disease evolution is characterized by increasing fibrosis and cirrhosis in a subset of patients, and a degree of fibrosis linked with increased risk of mortality.; MedDRA version: 20.0Level: LLTClassification code 10031743Term: Other chronic nonalcoholic liver diseaseSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: PTClassification code 10019708Term: Hepatic steatosisSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: LLTClassification code 10041970Term: Steatosis hepaticSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: HLTClassification code 10019669Term: Hepatic fibrosis and cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: PTClassification code 10019641Term: Hepatic cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: LLTClassification code 10009211Term: Cirrhosis liverSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: LLTClassification code 10024667Term: Liver cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: LLTClassification code 10009213Term: Cirrhosis of liverSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.1Level: LLTClassification code 10064704Term: Decompensated cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders

• Registration Number: EUCTR2018-004449-18-PL
• Lead Sponsor: Promethera Biosciences

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-19
• Last Update Posted: 3 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Able and willing to provide written informed consent and comply with the requirements of this study protocol
2. Age 18 to 70-years old, inclusive
3. Proven diagnosis of NASH based on histological evidence from biopsy performed within 6 months for F3 patients and within 2 years for F4 patients prior to Screening
If no biopsy is available within these time windows, a biopsy should be performed at Screening
NB: For F4 patients for whom the biopsy cannot confirm the diagnosis of NASH, any other causes of underlying liver diseases should be excluded

Infusion eligibility criteria
1. Fibrinogen > 80 mg/dL
2. And Platelets > 40.000/mm3
3. Absence thrombosis of the portal vein
4. No clinically significant reaction during previous infusions of IMP that, according to investigator, preclude the administration of HepaStem

Inclusion criteria for sub-study
1. Able and willing to provide written informed consent for the sub-study and comply the inclusion/exclusion of the study.
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

1. Alanine aminotransferase (ALT) = 8 x upper limit of normal (ULN)
2. Alcoholic liver disease or alcohol consumption exceeding the daily intake of 140g/w (two doses) for women and of 210g/w (three doses) for men
3. Other causes of liver disease including, but not limited to, alcoholic liver disease, active hepatitis B (HbsAg+), hepatitis C (PCR positive), autoimmune disorders, drug-induced hepatotoxicity, Wilson disease, hemochromatosis, and alpha-1-antitryspin deficiency based on medical history and/ or clinical and biological assessment
4. Recent recurrent or ongoing thrombotic or bleeding events within 3 months prior the screening
5. Patients considered at persistent risk of thrombosis or bleeding at the time of screening
6. Patients with high risk of Gastro intestinal bleeding at time of the screening. Patients with liver stiffness = 21 kPa at the time of the screening must have endoscopic assessment of variceal bleeding risk; presence of grade III or IV varices is an exclusion criterion, unless treated with primary prophylaxis
7. Heart failure (grade III and IV of New York Heart Association (NYHA) classification)
8. Major invasive procedure within 4 weeks prior to screening. The proper healing of the puncture site should be verified by the investigator
9. Cerebrovascular, myocardial, or limb arterial thrombotic event within 12 months prior to the screening and/or not considered stabilized by the investigator
10. Bariatric surgery within 1 year prior to the screening
11. Coagulation disturbances defined as (Drolz et al. 2016, Nadim et al. 2016, Stravitz et al. 2018, Green et al. 2018): fibrinogen at < 80 mg/dL and/or platelets at < 40 x 10³/mm3
12. Severe hepatic encephalopathy (defined by West Haven grade > 2)
13. Acute Decompensation of cirrhosis with Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD) score > 60
14. Acute on Chronic liver failure (ACLF) grade 1, 2 ,3
15. MELD score > 20
16. Child Pugh score = C
17. Septic shock or serious – non-controlled bacterial or systemic fungal infection defined as persistent or recent (< 48hrs) clinical signs of infection despite adequate antibiotic therapy
18. Circulatory failure defined as treated with vasoconstrictors to maintain arterial pressure or inotropes to improve cardiac output
19. Respiratory disorders with pulse oximetry < 90% and related clinical signs
20. Receiving one of the following treatments at the time of Screening:
a. Vitamin E, thiazolidinediones (TZD), glucagon-like peptide-1 (GLP1) antagonists, unless the dose is stable for 3 months prior to Screening
b. Drugs with any influence on coagulation: antiplatelet agents, anticoagulants (vitamin K antagonists, direct and parenteral anticoagulants, dual antiplatelet therapy)
Prophylaxis treatment with aspirin is authorized
21. Uncontrolled diabetes mellitus (HbA1c > 9.5 %) or/and known diabetic proliferative retinopathy
22. Seropositive to Human Immunodeficiency Virus (HIV)
23. Previous organ transplantation
24. Patients receiving immunosuppressive drugs
25. Malignancies, other than cured skin cancer, or cancer treated unless a complete remission over last 5 years is documented, or cancer considered as definitive cured by the investigator
26. Current or a history of hepatocellular carcinoma or serum alpha-fetoprotein > 200 ng/mL (Bruix, Sherman and Practice Guidelines Committee 2005, Omata et al. 2010)
27. Previous treatment with mesenchymal stem cells (MSCs) or other cell therapies be

Study & Design

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