HEP101 is a clinical study designed for patients suffering from Acute on Chronic Liver Failure (ACLF). ACLF patients will receive 4 infusions of HepaStem within 2 weeks. They will be monitored at Day 28, Month 3 and Year 1 post first HepaStem infusion.

Phase 1

• Conditions: Acute-on-chronic liver failure (ACLF) combines an acute deterioration of liver function in an individual with pre-existing chronic liver disease and extrahepatic organ failures. It is characterized by high short-term mortality (28-day mortality rate: 30-40%). Alcoholism and infection are the most frequent precipitating events. The development of ACLF is associated with exacerbated systemic inflammation that may indeed cause organ failures.; MedDRA version: 20.0Level: LLTClassification code 10008954Term: Chronic liver disease and cirrhosisSystem Organ Class: 100000004871; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]; MedDRA version: 20.1Level: LLTClassification code 10049844Term: Acute liver failureSystem Organ Class: 100000004871

• Registration Number: EUCTR2016-001177-32-FR
• Lead Sponsor: Promethera Biosciences

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-17
• Last Update Posted: 15 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Adult aged between 18 and 70 year old.

2. Informed Consent.
N.B: In case of hepatic encephalopathy, Informed Consent must be signed by patient’s legal representative according to local regulation, and by the patient, if possible, after encephalopathy improvement.

3. Cirrhosis as diagnosed by (1) liver histology or (2) by clinical and imaging examination (may include fibroscan).

4. ACLF Grade 1 or ACLF Grade 2 with the following restrictions
ACLF grade 1 eligible subset:
- liver failure plus cerebral and/or kidney dysfunction
- renal failure plus cerebral dysfunction
- cerebral failure plus kidney dysfunction
- coagulation failure plus cerebral and/or kidney dysfunction
Or
ACLF grade 2 eligible subset:
Any combination of 2 organ failures including: liver failure, renal failure, cerebral failure, coagulation failure.

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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Absence of portal vein flow as assessed by Doppler ultrasound or other exam.
2. Known prothrombotic disease or medical history of thrombotic events.
3. Gastrointestinal hemorrhage requiring blood transfusion unless controlled for more than 48h.
4. Septic shock or non-controlled bacterial infection defined as persistent clinical signs of infection despite adequate antibiotic therapy for more than 48h.
5. Clinical evidence of aspergilus infection.
6. Circulatory failure defined as treated with vasoconstrictors to maintain arterial pressure or inotropes to improve cardiac output. N.B: Use of terlipressine to control increased levels of creatinine is not an exclusion criteria.
7. Respiratory disordered with pulse oximetry < 93% and related clinical signs, requiring or not mechanical ventilation.
8. Treatment with corticosteroids for acute liver disease within 2 weeks before HepaStem infusion.
9. MELD score > 35.
10. Previous organ transplantation and/or ongoing immunosuppressive treatments.
11. Postoperative-decompensation following hepatectomy.
12. Renal failure due to chronic kidney disease.
13. Clinically significant left-right cardiac shunt.
14. Known or suspected hypersensitivity or allergy to any of the components of the HepaStem Diluent (human albumin, heparin sodium and sodium bicarbonate) or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.
15. Malignancies, other than curatively treated skin cancer, unless a complete remission over 5 years.
16. Refusal of abstinence from alcohol for at least 5 weeks from the study enrolment.
17. Pregnancy (negative ß-HCG test required) or women with childbearing potential who decline to use reliable contraceptive methods during the study.
18. Participation to any other interventional study within the last 4 weeks.
19. 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.

Study & Design

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