A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation.
ACLF, acute-on-chronic liver failure
AD, acute decompensation of liver cirrhosis
AE, adverse event
AESI, AE of special interest
ATMP, advanced therapy medicinal product
Alcoholic liver disease
BW, body weight
CRP, C-reactive protein
EASL-CLIF, European Association for the Study of Chronic Liver Failure
HALPC, human allogeneic liver-derived progenitor cells
INR, international normalised ratio
Liver regenerative medicine
MELD, model for end-stage liver disease
MSC, mesenchymal stem cells
SAE, serious AE
SAS, safety analysis set
SUSAR, suspected unexpected serious adverse reaction
Stem cell
TEG, thromboelastography
TGT, thrombin generation test
i.v., intravenous
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
22
09
2020
revised:
16
03
2021
accepted:
07
04
2021
entrez:
25
6
2021
pubmed:
26
6
2021
medline:
26
6
2021
Statut:
epublish
Résumé
Human allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD). This open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3. The 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×10 The treatment of patients with ACLF or AD with up to 2 doses of 1.2×10 EudraCT 2016-001177-32. Patients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
Human allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD).
METHODS
METHODS
This open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3.
RESULTS
RESULTS
The 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×10
CONCLUSIONS
CONCLUSIONS
The treatment of patients with ACLF or AD with up to 2 doses of 1.2×10
CLINICAL TRIALS REGISTRATION
BACKGROUND
EudraCT 2016-001177-32.
LAY SUMMARY
BACKGROUND
Patients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy.
Identifiants
pubmed: 34169246
doi: 10.1016/j.jhepr.2021.100291
pii: S2589-5559(21)00067-7
pmc: PMC8207211
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100291Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
NC-C, IS, NG, YV, SM, and VB are employees of Promethera Biosciences. MN is a founder, patent holder, and consultant of Promethera Biosciences and employee of UCLouvain. ES is a founder, patent holder, consultant and board member of Promethera Biosciences and employee of UCLouvain. TG is an advisory board member for Promethera Biosciences and for Goliver Therapeutics, and is a recipient of a grant from Gilead Sciences Inc. FN, P-FL, LL, LH, VV, DL, and AA report no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.
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