Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences)(Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences))

概要

基本信息

药物类型

间充质干细胞疗法

别名

HHALPC、HepaStem、Heterologous Human Adult Liver derived Progenitor Cells

+ [1]

靶点-

作用机制

软骨替代物、细胞替代物、骨生成刺激剂

+ [1]

治疗领域

消化系统疾病肿瘤

在研适应症

肝硬化肿瘤

非在研适应症

瓜氨酸血症肝功能衰竭N-乙酰谷氨酸合成酶缺乏症+ [3]

原研机构

Facultés Universitaires Catholiques de Mons

在研机构

PROMETHERA Biosciences SA

非在研机构-

最高研发阶段临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

17

项与 Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) 相关的临床试验

KCT0003619 / Withdrawn临床2期

A prospective, open-label study of the safety and efficacy of Hepastem infusion in pediatric patients with urea cycle disorders.

开始日期2020-10-01

申办/合作机构

HLB Cell Co., Ltd.

EUCTR2019-003051-11-NL / Not yet recruiting临床2期

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) - DHELIVER - HEP102 - DHELIVER

开始日期2020-04-20

申办/合作机构-

NCT04229901 / Terminated临床2期

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.

开始日期2020-01-21

申办/合作机构

Cellaïon SA

100 项与 Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) 相关的临床结果

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100 项与 Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) 相关的转化医学

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100 项与 Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) 相关的专利（医药）

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4

项与 Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) 相关的文献（医药）

2021-08-01·JHEP Reports

A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation

Article

作者: Albillos, Agustin ; Sokal, Etienne M ; Lasser, Luc L ; Gustot, Thierry ; Vainilovich, Yelena ; Michel, Sébastien ; Najimi, Mustapha ; Stoykov, Ivaylo ; Lyubomirova, Desislava ; Gordillo, Noelia ; Nevens, Frederik ; Vargas, Victor ; Clerget-Chossat, Nathalie ; Haralampiev, Lyudmil E ; Laterre, Pierre-François ; Barthel, Virginie

BACKGROUND & AIMSHuman 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).METHODSThis 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.RESULTSThe 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 (∼5×10⁶ 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 1.2×10⁶ 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.CONCLUSIONSThe treatment of patients with ACLF or AD with up to 2 doses of 1.2×10⁶ 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.CLINICAL TRIALS REGISTRATIONEudraCT 2016-001177-32.LAY SUMMARYPatients 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.

2020-12-01·Stem Cell Research & Therapy2区 · 医学

Infusion-related thrombogenesis by liver-derived mesenchymal stem cells controlled by anticoagulant drugs in 11 patients with liver-based metabolic disorders

2区 · 医学

ArticleOA

作者: Stéphenne, Xavier ; Sokal, Etienne E M ; Ambroise, Jérome ; Coppin, Louise C F ; Smets, Françoise

AbstractBackgroundMesenchymal stem cell (MSC) transplantation is a fast-developing therapy in regenerative medicine. However, some concerns have been raised regarding their safety and the infusion-related pro-coagulant activity. The aim of this study is to analyze the induced thrombogenic risk and the safety of adding anticoagulants during intraportal infusions of liver-derived MSCs (HepaStem), in patients with Crigler-Najjar (CN) and urea cycle disorders (UCD).MethodsEleven patients (6 CN and 5 UCD patients) were included in this partially randomized phase 1/2 study. Three cell doses of HepaStem were investigated: low (12.5 × 106 cells/kg), intermediate (50 × 106 cells/kg), and high doses (200 × 106 cells/kg). A combination of anticoagulants, heparin (10 I.U./5 × 106cells), and bivalirudin (1.75 mg/kg/h) were added during cell infusions. The infusion-related thrombogenic risk and anticoagulation were evaluated by clinical monitoring, blood sampling (platelet and D-dimer levels, activated clotting time, etc.) and liver Doppler ultrasound. Mixed effects linear regression models were used to assess statistically significant differences.ResultsOne patient presented a thrombogenic event such as a partial portal vein thrombus after 6 infusions. Minor adverse effects such as petechiae, epistaxis, and cutaneous hemorrhage at the site of catheter placement were observed in four patients. A significant decrease in platelet and increase in D-dimer levels were observed at the end of the infusion cycle, normalizing spontaneously after 7 days. No significant and clinically relevant increase in portal vein pressure could be observed once the infusion cycle was completed.ConclusionsThe safety- and the infusion-related pro-coagulant activity remains a concern in MSC transplantation. In our study, a combination of heparin and bivalirudin was added to prevent the thrombogenic risk induced by HepaStem infusions in 11 patients. A significant decrease in platelet and increase in D-dimer levels were observed, suggesting the activation of coagulation in these patients; however, this was spontaneously reversible in time. We can conclude that adding this combination of anticoagulants is safe and limits infusion-related thrombogenesis to subclinical signs in most of the patients.Trial registrationClinicalTrials.gov identifier: NCT01765283—January 10, 2013

2019-09-01·Transplantation2区 · 医学

Phase I/II Trial of Liver–derived Mesenchymal Stem Cells in Pediatric Liver–based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

2区 · 医学

Article

作者: Grunewald, Stephanie ; Binda, Maria Mercedes ; McKiernan, Patrick ; Clapuyt, Philippe ; Belmonte, Nathalie ; de Vos, Beatrice ; Mandel, Hanna ; Kamińska, Diana ; Smets, Françoise ; Gonçalves, Isabel ; Dobbelaere, Dries ; Lopes, Ana Isabel ; Gissen, Paul ; Torre, Giuliano ; Najimi, Mustapha ; Eyskens, François ; Pawlowska, Joanna ; Yudkoff, Marc ; Thonnard, Joelle ; Pariente, Danièle ; Jacquemin, Emmanuel ; Sokal, Etienne ; Dionisi-Vici, Carlo ; Shteyer, Eyal ; Shapiro, Riki ; Broué, Pierre

Background.Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.Objective.This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy.Methods.Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis.Results.The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases.Conclusions.This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.

100 项与 Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肝功能衰竭	临床1期	保加利亚	PROMETHERA Biosciences SA	2016-03-30
肝功能衰竭	临床1期	法国	PROMETHERA Biosciences SA	2016-03-30
鸟氨酸氨基甲酰基转移酶缺乏症	临床1期	比利时	PROMETHERA Biosciences SA	2014-07-01
鸟氨酸氨基甲酰基转移酶缺乏症	临床1期	法国	PROMETHERA Biosciences SA	2014-07-01
尿素循环障碍	临床1期	葡萄牙	PROMETHERA Biosciences SA	2013-03-19
瓜氨酸血症	临床1期	英国	PROMETHERA Biosciences SA	2012-11-30
瓜氨酸血症	临床1期	法国	PROMETHERA Biosciences SA	2012-11-30
瓜氨酸血症	临床1期	比利时	PROMETHERA Biosciences SA	2012-11-30
N-乙酰谷氨酸合成酶缺乏症	临床1期	英国	PROMETHERA Biosciences SA	2012-11-30
N-乙酰谷氨酸合成酶缺乏症	临床1期	比利时	PROMETHERA Biosciences SA	2012-11-30

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01765283 (HEP001, Pubmed \| Transplantation) 人工标引	临床1/2期	尿素循环障碍 \| 代谢性疾病 \| Crigler-Najjar综合征	20	HepaStem	(鏇壓齋鬱餘廠襯蓋壓憲) = 鏇壓繭願築鹹簾鏇夢築鬱淵顧網艱壓壓醖鏇衊 (夢鹹願築憲選襯鏇構衊 ) 更多	积极	2019-09-01