TY - JOUR
T1 - A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation
AU - Nevens, Frederik
AU - Gustot, Thierry
AU - Laterre, Pierre-François
AU - Lasser, Luc L.
AU - Haralampiev, Lyudmil E.
AU - Vargas Blasco, Víctor
AU - Lyubomirova, Desislava
AU - Albillos, Agustín
AU - Najimi, Mustapha
AU - Michel, Sébastien
AU - Stoykov, Ivaylo
AU - Gordillo, Noelia
AU - Vainilovich, Yelena
AU - Barthel, Virginie
AU - Clerget-Chossat, Nathalie
AU - Sokal, Etienne M.
PY - 2021
Y1 - 2021
N2 - 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
AB - 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
KW - Alcoholic liver disease
KW - Stem cell
KW - Liver regenerative medicine
KW - ACLF, acute-on-chronic liver failure
KW - AD, acute decompensation of liver cirrhosis
KW - AE, adverse event
KW - AESI, AE of special interest
KW - ATMP, advanced therapy medicinal product
KW - BW, body weight
KW - CRP, C-reactive protein
KW - EASL-CLIF, European Association for the Study of Chronic Liver Failure
KW - HALPC, human allogeneic liver-derived progenitor cells
KW - INR, international normalised ratio
KW - I.v., intravenous
KW - MELD, model for end-stage liver disease
KW - MSC, mesenchymal stem cells
KW - SAE, serious AE
KW - SAS, safety analysis set
KW - SUSAR, suspected unexpected serious adverse reaction
KW - TEG, thromboelastography
KW - TGT, thrombin generation test
U2 - 10.1016/j.jhepr.2021.100291
DO - 10.1016/j.jhepr.2021.100291
M3 - Article
C2 - 34169246
SN - 2589-5559
VL - 3
JO - JHEP Reports
JF - JHEP Reports
ER -
