Safety and Tolerability of HepaStem in Patients With Cirrhotic and Pre-cirrhotic NASH Patients (PANASH)

Multicenter, Open-label, Safety and Tolerability Study of Ascending Doses of HepaStem in Patients With Cirrhotic and Pre-cirrhotic Non-alcoholic Steato-hepatitis (NASH)

Multicenter, open-label, safety and tolerability study of ascending doses of HepaStem in patients with cirrhotic and pre-cirrhotic non-alcoholic steato-hepatitis (NASH) to determine the safety and tolerability of ascending single and repeated doses of HepaStem administered to patients with cirrhotic and pre-cirrhotic non-alcoholic steato-hepatitis (NASH)

Study Overview

• Status: Completed
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: HepaStem

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1070
    • CUB Erasme
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St Luc
  • Edegem, Belgium, 2650
    • University Hospital Antwerp (UZA)
  • Gent, Belgium, 9000
    • UZ Gent
• Bulgaria
  • Sofia, Bulgaria, 1527
    • University Multiprofile Hospital for Active Treatment "Tsaritsa Yoana - ISUL"
  • Sofia, Bulgaria, 1606
    • Multiprofile hospital for active treatment (MHAT) Sofia Military Medical Academy
  • Stara Zagora, Bulgaria, 6004
    • Trakia Park Hospital
• France
  • Bordeaux, France, 33604
    • CHU Bordeaux
  • Villejuif, France, 94804
    • PAUL BROUSSE HOSPITAL
• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Able and willing to provide written informed consent and comply with the requirements of this study protocol
• Age 18 to 70-years old, inclusive
• 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

Main Exclusion Criteria:

• 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
• 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
• Recent recurrent or ongoing thrombotic or bleeding events within 3 months prior the screening
• Patients considered at persistent risk of thrombosis or bleeding at the time of screening
• Patients with high risk of Gastro intestinal bleeding at time of the screening.
• Cerebrovascular, myocardial, or limb arterial thrombotic event within 12 months prior to the screening and/or not considered stabilized by the investigator
• Bariatric surgery within 1 year prior to the screening
• 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
• Severe hepatic encephalopathy (defined by West Haven grade > 2)
• Acute Decompensation of cirrhosis with Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD) score > 60
• Acute on Chronic liver failure (ACLF) grade 1, 2 ,3
• MELD score > 20
• Child Pugh score ≥ C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: F4 patient population; A total of 2 doses are planned to be administered as single or repeated infusions in an ascending manner:	Drug: HepaStem; Heterologous human adult liver-derived progenitor cells
Experimental: F3 patient population; A total of 2 doses are planned to be administered as single or repeated infusions in an ascending manner:	Drug: HepaStem; Heterologous human adult liver-derived progenitor cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Event	Safety and Tolerability	up to Day 28

Collaborators and Investigators

• Sponsor: Promethera Therapeutics
• Investigators: Study Chair: Etienne SOKAL, MD, PhD, CSMO

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2019
• Primary Completion (Actual): May 28, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 24, 2019
• First Posted (Actual): May 28, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: NASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: HEP201

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