A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation
Nevens, Frederik (University Hospitals Leuven (Bèlgica))
Gustot, Thierry (C.U.B. Erasme Hospital)
Laterre, Pierre-François (Cliniques Universitaires Saint-Luc)
Lasser, Luc L. (CHU Brugmann)
Haralampiev, Lyudmil E. (Multiprofile Hospital for Active Treatment (MEDICA), Ruse)
Vargas, Victor (Hospital Universitari Vall d'Hebron)
Lyubomirova, Desislava (University Multiprofile Hospital for Active Treatment "Georgi Stranski")
Albillos, Agustín (Hospital Universitario Ramón y Cajal (Madrid))
Najimi, Mustapha (Institute of Experimental and Clinical Research, Brussels)
Michel, Sébastien (Promethera Biosciences, Mont-Saint-Guibert)
Stoykov, Ivaylo (Promethera Biosciences, Mont-Saint-Guibert)
Gordillo, Noelia (Promethera Biosciences, Mont-Saint-Guibert)
Vainilovich, Yelena (Promethera Biosciences, Mont-Saint-Guibert)
Barthel, Virginie (Promethera Biosciences, Mont-Saint-Guibert)
Clerget-Chossat, Nathalie (Promethera Biosciences, Mont-Saint-Guibert)
Sokal, Etienne M. (Cliniques Universitaires Saint-Luc, UCLouvain, Pediatric Hepatology & Gastroenterology Unit)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	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 6 cells/kg body weight [BW]) had severe adverse bleeding events attributed to treatment. In 21 patients subsequently treated with lower HALPC doses (0. 6 or 1. 2×10 6 cells/kg BW, 1 or 2 times 7 days apart), no serious adverse events were related to treatment, and the other adverse events were in line with those expected in patients with ACLF and AD. Overall, markers of systemic inflammation and altered liver function decreased gradually for the surviving patients. The Day-28 and Month-3 survival rates were 83% (20/24) and 71% (17/24), and at Month 3, no patient had ACLF. The treatment of patients with ACLF or AD with up to 2 doses of 1. 2×10 6 HALPC/kg BW appeared safe. The results of this study support the initiation of a proof-of-concept study in a larger cohort of patients with ACLF to further confirm the safety and evaluate the efficacy of HALPC therapy. 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.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alcoholic liver disease ; Stem cell ; Liver regenerative medicine ; 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 ; 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 ; I.v., intravenous ; MELD, model for end-stage liver disease ; MSC, mesenchymal stem cells ; SAE, serious AE ; SAS, safety analysis set ; SUSAR, suspected unexpected serious adverse reaction ; TEG, thromboelastography ; TGT, thrombin generation test
Publicat a:	JHEP Reports, Vol. 3 (april 2021) , ISSN 2589-5559

DOI: 10.1016/j.jhepr.2021.100291
PMID: 34169246

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