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

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

This is an interventional, double blind, randomized (2:1), and placebo-controlled study of 2 infusions of a 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute on Chronic Liver Failure
• Intervention / Treatment: Drug: HepaStem; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Development; Phone Number: +3210394300; Email: clinic@cellaion.com

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Belgium
  • Antwerp, Belgium
    • UZ Antwerpen
  • Brussels, Belgium
    • CHU Brugmann
  • Brussels, Belgium
    • CHU Erasme
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium
    • UZ Leuven
  • Liège, Belgium
    • Chc Montlegia
  • Woluwe-Saint-Lambert, Belgium
    • Cliniques Universitaires Saint-Luc
• Bulgaria
  • Pleven, Bulgaria
    • University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
  • Ruse, Bulgaria
    • UMHAT Medica
  • Sofia, Bulgaria
    • Military Medical Academy
  • Sofia, Bulgaria
    • UMHAT Sveta Anna
  • Sofia, Bulgaria
    • UMHAT Tzarita Joanna
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Regional Hospital
  • Tallinn, Estonia
    • Lääne-Tallinna Keskhaigla AS
• France
  • Angers, France
    • CHU Angers
  • Clichy, France
    • Hopital Beaujon
  • Créteil, France, 94000
    • Assistance Publique Hopitaux De Paris
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire Grenoble Alpes
  • Lyon, France
    • Hospices Civils de Lyon
  • Marseille, France
    • Assistance Publique Hopitaux de Marseille
  • Montpellier, France
    • CHU Montpellier
  • Paris, France
    • Assistance Publique-Hopitaux de Paris - Hopitaux Universitaires Pitie-Salpetriere
  • Strasbourg, France
    • Les Hôpitaux Universitaires de Strasbourg
  • Toulouse, France, 31059
    • CHU de Toulouse
  • Villejuif, France, 94804
    • Hospital Paul Brousse
• Germany
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Leipzig, Germany, 04103
    • University Hospital Of Leipzig
  • Ulm, Germany, 89081
    • University Hospital Of Ulm AöR
• Italy
  • Milan, Italy, 20162
    • Azienda Ospedaliera Ospedale Niguarda CA' Granda
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Friuli Centrale
• Latvia
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital
• Lithuania
  • Kaunas, Lithuania, 50161
    • Lietuvos Sveikatos Mokslų Universiteto Ligoninė Kauno Klinikos
• North Macedonia
  • Skopje, North Macedonia, 1000
    • PHI General City Hospital "8mi Septemvri"
  • Skopje, North Macedonia, 1000
    • PHI University Clinic of Gastroenterohepatology
• Poland
  • Mysłowice, Poland, 41-400
    • ID Clinic
  • Rzeszów, Poland, 35-301
    • Kliniczny Szpital Wojewódzki Nr 2 Im. Św. Jadwigi Królowej W Rzeszowie
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • F.D. Roosevelt University General Hospital Of Banská Bystrica
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28049
    • University Hospital Ramón Y Cajal
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • Sabadell, Spain, 08208
    • Sabadell Hospital
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano Blesa
  • Zaragoza, Spain, 50009
    • Hospital Unviersitario Miguel Servet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Are adults aged between 18 and 75 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.

Main Exclusion Criteria:

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:

   • fibrinogen < 80 mg/dL
   • 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%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients in the placebo arm will receive 2 infusions of placebo (i.v) (7 day interval)	Drug: Placebo; Placebo will be administered as an intravenous (IV) infusion
Experimental: HepaStem; Patients in the HepaStem arm will receive 2 infusions of HepaStem (i.v) at 1.0 million of cells/kg of total body weight (7 day interval)	Drug: HepaStem; HepaStem will be administered as an intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Whether the patients are still alive will be recorded up to Day 90. Time and reason of death will be recorded.	Day 90

Secondary Outcome Measures

Outcome Measure	Time Frame
Liver transplant-free survival	Day 90
Transplant-free survival while free of ACLF	Day 90
Transplant-free survival with MELD-Na score < 15	Day 90
Duration of overall hospitalization and hospitalization in ICU and non-ICU during the index hospitalization	up to Day 90

Collaborators and Investigators

• Sponsor: Cellaion SA

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 11, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ACLF; Hepastem; HALPC
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: HEP102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No