Efficacy and Safety of BMSCs (CG-BM1) for ACLF Patients

Efficacy and Safety of Allogeneic Human Bone Marrow Mesenchymal Stem Cells for the Treatment of Patients with Acute-on-chronic Liver Failure

The goal of this clinical trial is to learn if CG-BM1 Allogeneic Human Bone Marrow Mesenchymal Stem Cell Injection (hereinafter referred to as CG-BM1) can treat acute-on-chronic liver failure (ACLF) patients. Main purposes of this clinical trial are:

• To evaluate the safety and tolerability of CG-BM1 for the treatment of adult patients with ACLF.
• To observe the preliminary effectiveness of CG-BM1 in treating adult ACLF patients, and to provide a basis for subsequent clinical trial protocol design.

Study Overview

• Status: Recruiting
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Drug: Solvent of CG-BM1; Drug: Bone marrow mesenchymal stem cells (low dose); Drug: Bone marrow mesenchymal stem cells (medium dose); Drug: Bone marrow mesenchymal stem cells (high dose)

Detailed Description

CG-BM1 is a bone marrow mesenchymal stem cell product independently developed by Guangzhou Cellgenes Biotechnology Co., Ltd. The active ingredient of CG-BM1 is human bone marrow mesenchymal stem cell, which is derived from bone marrow donated by healthy adults and prepared into stem cell injection under aseptic conditions. CG-BM1 is the first bone marrow mesenchymal stem cell (BMSC) therapeutic drug for the treatment of ACLF in China. Preclinical data showed that CG-BM1 has the ability to immunomodulate, inhibit the secretion of pro-inflammatory factors by immune cells, and up-regulate the level of anti-inflammatory factors, which can significantly improve the liver function, reduce the inflammatory response, and reverse hepatic fibrosis in ACLF animal models, and the results of the study suggest that it is safe and effective, supporting its further clinical development. The purpose of this study was to evaluate the safety and tolerability of CG-BM1 for the treatment of patients with ACLF, as well as to evaluate the preliminary efficacy of CG-BM1 for the treatment of patients with ACLF.

The study was divided into 2 phases, the first with an open-labeled, dose-escalation design; the second with a multicenter, randomized, double-blind, placebo-controlled design. Phase I: Patients was divided into three dose groups using a traditional "3+3" design. 3-6 subjects were enrolled in each dose. Phase II: Multiple-dose, randomized, double-blind, placebo-controlled trial. Based on the results of the phase I trial, two dose groups were selected for phase II.

A total of 90 subjects were enrolled and randomized 1:1:1. The experiment group received CG-BM1 + conventional treatment regimen, and the control group received placebo + conventional treatment regimen.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bingliang Lin, MD; Phone Number: 86-020-85253165; Email: linbingl@mail.sysu.edu.cn
• Study Contact Backup: Name: Junfeng Chen, MD; Phone Number: 86-020-85253165; Email: chenjf36@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Third Affliated Hospital of Sun Yat-sen University
      • Contact: Bingliang Lin, MD; Phone Number: 86-20-85253165; Email: linbingl@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Phase I:

Inclusion Criteria:

1. Voluntarily participate in the clinical study. The patient or legal guardian fully understands and is informed about the study and signs an informed consent form. Willing to follow and be able to complete all trial procedures.
2. Age ≥18 years old, male or female.
3. Diagnostic criteria in accordance with the Guidelines for Diagnosis and Treatment of Liver Failure (2018 edition) issued by the Liver Failure and Artificial Liver Group of the Infectious Diseases Branch of the Chinese Medical Association and the Liver Disease Branch of the Chinese Medical Association Diagnostic criteria, specific indicators include 1) Suffering from the basis of chronic liver disease; 2) Serum TBIL 171 μ mol/l or mean daily rise ≥17.1 μmol/L; 3) Meeting any of the following three: i. Having a bleeding tendency; ii. Comorbid hepatic encephalopathy; iii. Comorbid hepatorenal syndrome.
4. The cause of liver failure is unlimited.
5. Model for End Stage Liver Disease (MELD) score under 30.

6. No conception (or conception of sexual partner) during the study period (from signing of informed consent to the last visit) and within 6 months after the last cell infusion; and childbearing, or breastfeeding potential, including:

   • Female subject with persistent spontaneous menopause >12 months or who have undergone sterilization (e.g., tubal ligation or bilateral oophorectomy or hysterectomy).
   • Non-menopausal female subject with a negative serum pregnancy test within 7 days prior to the first cellular infusion. Sign an informed consent and willingness to use one of the following effective methods of contraception, including intrauterine device (IUD), tubal ligation, double barrier method (condom, vaginal diaphragm, spermicide) and spermicide for the male partner, but does not include oral contraceptives, for a period of 6 months after the last cellular infusion.
   • Male subjects who are willing to use one or more effective methods of contraception, including vasectomy, double-barrier methods, use of the pill by the female partner, intrauterine devices or tubal ligation from the time of the first infusion until 6 months after the last infusion.
   • Male or non-menopausal female subjects who do not have, or are willing to not have sexual intercourse during the study and for 6 months after the last cell infusion.

Exclusion Criteria:

1. Be allergic to known components of the drug (the main component of the product is bone marrow mesenchymal stem cells, excipients include dimethyl sulfoxide, human albumin) or other history of severe allergy.
2. Patients with severe infections such as septic shock.
3. Patients with gastrointestinal bleeding at the time of screening.
4. Hepatic encephalopathy grade 4.
5. Concurrent failure of 3 or more organs (liver failure defined as TBiL ≥12 mg/dl, renal failure defined as creatinine ≥2.0 mg/dl, coagulation failure defined as INR ≥2.5, cerebral failure defined as hepatic encephalopathy grades 3-4, circulatory failure defined by use of vasoactive drugs, and respiratory failure was defined as PaO2 /FiO2 ≤200 or SpO2 /FiO2 ≤214 or mechanical ventilation)
6. Pregnancy or breastfeeding.
7. Previous history of malignant tumors.
8. Imaging suggestive of intrahepatic nodular space-occupying lesions.
9. A history of immunodeficiency, including HIV-positive, or other acquired or congenital immunodeficiency diseases.
10. Patients with previous liver transplantation.
11. Deep vein thrombosis at screening or history of pulmonary embolism within 3 months prior to screening.
12. Patients with pulmonary hypertension.
13. History of myocardial infarction within 6 months.
14. Previous stem cell therapy.
15. Participation in another interventional clinical trial within 3 months or 5 half-lives (for experimental drug interventions only, whichever is longer) prior to infusion.
16. Any other factors that, in the judgment of the investigator, make the subject inappropriate for participation in this trial.

Phase II:

Inclusion Criteria:

Inclusion Criteria:

1. Voluntarily participate in the clinical study. The patient or legal guardian fully understands and is informed about the study and signs an informed consent form. Willing to follow and be able to complete all trial procedures.
2. Age ≥18 years old, male or female.
3. Diagnostic criteria in accordance with the Guidelines for Diagnosis and Treatment of Liver Failure (2018 edition) issued by the Liver Failure and Artificial Liver Group of the Infectious Diseases Branch of the Chinese Medical Association and the Liver Disease Branch of the Chinese Medical Association Diagnostic criteria, specific indicators include 1) Suffering from the basis of chronic liver disease; 2) Serum TBIL 171 μ mol/l or mean daily rise ≥17.1 μmol/L; 3) Meeting any of the following three: i. Having a bleeding tendency; ii. Comorbid hepatic encephalopathy; iii. Comorbid hepatorenal syndrome.
4. The cause of liver failure is Hepatitis B.
5. Model for End Stage Liver Disease (MELD) score under 30.

6. No conception (or conception of sexual partner) during the study period (from signing of informed consent to the last visit) and within 6 months after the last cell infusion; and childbearing, or breastfeeding potential, including:

   • Female subject with persistent spontaneous menopause >12 months or who have undergone sterilization (e.g., tubal ligation or bilateral oophorectomy or hysterectomy).
   • Non-menopausal female subject with a negative serum pregnancy test within 7 days prior to the first cellular infusion. Sign an informed consent and willingness to use one of the following effective methods of contraception, including intrauterine device (IUD), tubal ligation, double barrier method (condom, vaginal diaphragm, spermicide) and spermicide for the male partner, but does not include oral contraceptives, for a period of 6 months after the last cellular infusion.
   • Male subjects who are willing to use one or more effective methods of contraception, including vasectomy, double-barrier methods, use of the pill by the female partner, intrauterine devices or tubal ligation from the time of the first infusion until 6 months after the last infusion.
   • Male or non-menopausal female subjects who do not have, or are willing to not have sexual intercourse during the study and for 6 months after the last cell infusion.

Exclusion Criteria:

1. Be allergic to known components of the drug (the main component of the product is bone marrow mesenchymal stem cells, excipients include dimethyl sulfoxide, human albumin) or other history of severe allergy.
2. Patients with severe infections such as septic shock.
3. Patients with gastrointestinal bleeding at the time of screening.
4. Hepatic encephalopathy grade 4.
5. Concurrent failure of 3 or more organs (liver failure defined as TBiL ≥12 mg/dl, renal failure defined as creatinine ≥2.0 mg/dl, coagulation failure defined as INR ≥2.5, cerebral failure defined as hepatic encephalopathy grades 3-4, circulatory failure defined by use of vasoactive drugs, and respiratory failure was defined as PaO2 /FiO2 ≤200 or SpO2 /FiO2 ≤214 or mechanical ventilation)
6. Pregnancy or breastfeeding.
7. Previous history of malignant tumors.
8. Imaging suggestive of intrahepatic solid nodal space-occupying lesions and which the investigator determines may compromise subject safety.
9. Received artificial liver therapy within 7 days prior to first dose.
10. A history of immunodeficiency, including HIV-positive, or other acquired or congenital immunodeficiency diseases.
11. Patients with previous liver transplantation.
12. Deep vein thrombosis at screening or history of pulmonary embolism within 3 months prior to screening.
13. Patients with pulmonary hypertension.
14. History of myocardial infarction within 6 months.
15. Previous stem cell therapy.
16. Participation in another interventional clinical trial within 3 months or 5 half-lives (for experimental drug interventions only, whichever is longer) prior to infusion.
17. Any other factors that, in the judgment of the investigator, make the subject inappropriate for participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Phase 2: Placebo Control; The control group received placebo + conventional treatment. Placebo was solubilizer of CG-BM1. Conventional treatment included hepatoprotection, antiviral therapy or other etiologic treatments, supplementation of plasma and albumin, supplementation of coagulation factors, treatment of complications, and nutritional support.	Drug: Solvent of CG-BM1; Administered intravenously, once a week for a total of 4 doses.
Experimental: Phase 2: Low Dose Group; Patients in low dose group receive CG-BM1 + conventional treatment. Administration procedure of CG-BM1 is 1.0×10^6 cells/kg CG-BM1 once a week for a total of 4 administrations.	Drug: Bone marrow mesenchymal stem cells (low dose); Administered intravenously. For phase I: single infusion, 1.0×10^6 cells/kg. For phase II: 1.0×10^6 cells /kg once a week for a total of 4 times.; Other Names: CG-BM1
Experimental: Phase 2: Medium Dose Group; Patients in medium dose group receive CG-BM1 + conventional treatment. Administration procedure of CG-BM1 is 2.0×10^6 cells/kg CG-BM1 once a week for a total of 4 administrations.	Drug: Bone marrow mesenchymal stem cells (medium dose); Administered intravenously. For phase I: single infusion, 2.0×10^6 cells /kg. For phase II: 2.0×10^6 cells /kg once a week for a total of 4 times.
Experimental: Phase 1: Low Dose Group; The trial group with a low dose (1.0×10^6 cells/kg) will first enroll one subject, who will be infused with single dose CG-BM1 and then observed for at least 28 days. The clinical data of the first subject will be reviewed by the SRC.; If the first subject in the low-dose trial group experiences DLT, enrollment will be suspended. After discussion, recommendations will be made. If the trial is to continue, two additional subjects will be enrolled for observation. If no DLT occurs, the dose trial group will need to enroll three more subjects.; If the first subject in the dose trial group does not experience DLT after 28 days, - the remaining two subjects in that dose trial group will be enrolled. Once all subjects in the dose trial group have completed the infusion and have been observed for 28 days, the clinical data of all subjects will be submitted to the SRC. After a comprehensive evaluation, the SRC will provide recommendations for dose escalation.	Drug: Bone marrow mesenchymal stem cells (low dose); Administered intravenously. For phase I: single infusion, 1.0×10^6 cells/kg. For phase II: 1.0×10^6 cells /kg once a week for a total of 4 times.; Other Names: CG-BM1
Experimental: Phase 1: Medium Dose Group; The trial group with a low dose (2.0×10^6 cells/kg) will first enroll one subject, who will be infused with single dose CG-BM1 and then observed for at least 28 days. The clinical data of the first subject will be reviewed by the SRC.; If the first subject in the low-dose trial group experiences DLT, enrollment will be suspended. After discussion, recommendations will be made. If the trial is to continue, two additional subjects will be enrolled for observation. If no DLT occurs, the dose trial group will need to enroll three more subjects.; If the first subject in the dose trial group does not experience DLT after 28 days, - the remaining two subjects in that dose trial group will be enrolled. Once all subjects in the dose trial group have completed the infusion and have been observed for 28 days, the clinical data of all subjects will be submitted to the SRC. After a comprehensive evaluation, the SRC will provide recommendations for dose escalation.	Drug: Bone marrow mesenchymal stem cells (medium dose); Administered intravenously. For phase I: single infusion, 2.0×10^6 cells /kg. For phase II: 2.0×10^6 cells /kg once a week for a total of 4 times.
Experimental: Phase 1: High Dose Group; The trial group with a low dose (4.0×10^6 cells/kg) will first enroll one subject, who will be infused with single dose CG-BM1 and then observed for at least 28 days. The clinical data of the first subject will be reviewed by the SRC.; If the first subject in the low-dose trial group experiences DLT, enrollment will be suspended. After discussion, recommendations will be made. If the trial is to continue, two additional subjects will be enrolled for observation. If no DLT occurs, the dose trial group will need to enroll three more subjects.; If the first subject in the dose trial group does not experience DLT after 28 days, - the remaining two subjects in that dose trial group will be enrolled. Once all subjects in the dose trial group have completed the infusion and have been observed for 28 days, the clinical data of all subjects will be submitted to the SRC. After a comprehensive evaluation, the SRC will provide recommendations for dose escalation.	Drug: Bone marrow mesenchymal stem cells (high dose); Administered intravenously. For phase I: single infusion, 4×10^6 cells /kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Incidence of CG-BM1-related dose-limiting toxicity (DLT) events	Incidence of CG-BM1-related DLT events.	From first dose to 180 days after the first dose.
Phase I: Adverse event related to CG-BM1 treatment	Any adverse event related to CG-BM1 treatment that occurred during the study period.	From first dose to 180 days after the first dose.
Phase II: Liver transplant-free survival	90-day liver transplant-free survival.	90 day after the first dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Liver transplant-free survival	28-day, 90-day, and 180-day liver transplant-free survival.	28 day, 90 day, and 180 days after the first dose.
Phase I: Changes of aspartate aminotransferase (AST)	Amount of increase or decrease in serum AST.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes of alanine aminotransferase (ALT)	Amount of increase or decrease in serum ALT.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes of albumin	Amount of increase or decrease in serum albumin.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes of alkaline phosphatase (ALP)	Amount of increase or decrease in serum ALP.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes of γ-glutamyl transpeptidase (GGT)	Amount of increase or decrease in serum GGT.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes of total bilirubin (TBil)	Amount of increase or decrease in serum TBil.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes of international normalized ratio (INR)	Amount of increase or decrease in INR.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.
Phase I: Changes in liver stiffness measurement (LSM) values	Changes in LSM values measured by transient elastography (TE).	Pre-treatment, 14 days, 28 days, 60 days, 90 days after the first dose.
Phase I: Changes of 15-minute retention rate obtained by indocyanine green (ICG) retention test	Changes of 15-minute retention rate obtained by indocyanine green (ICG) retention test. Inject indocyanine green (ICG) rapidly into a peripheral vein on one side of the patient at a dose of 0.5mg/kg body weight, and start timing immediately after the injection. After 15 minutes, draw 2ml of blood from the opposite side peripheral vein, separate the serum, and measure the concentration of indocyanine green using a spectrophotometer. Calculate the indocyanine green retention rate at 15 minutes using the following formula: ICG Retention Rate (%) = (C15 mg% ÷ 1 mg%) × 100%.	Pre-treatment, 7 days, 14 days, 28 days, 60 days, 90 days after the first dose.
Phase I: Complication rate	Complication rate within 180 days.	180 days after the first dose.
Phase I: Changes in chronic liver failure consortium organ failure score (CLIF-C OFs)	Changes in CLIF-C OFs. Each organ system is scored on a scale to generate the overall CLIF-C OF score, ranging from 0 to 18. The higher the CLIF C OF score, the poorer the prognosis for the patient, which means a higher short-term mortality rate.	Pre-treatment, 3 days, 7 days, 14 days, 28 days, 60 days, 90 days after the first dose.
Phase I: Changes in Model for end-stage liver disease (MELD) score	MELDScore = 10 * ((0.957 * ln(Creatinine)) + (0.378 * ln(Bilirubin)) + (1.12 * ln(INR))) + 6.43. An increase in the MELD score indicates worse liver function, poorer prognosis, and a higher urgency for liver transplantation.	Pre-treatment, 3 days, 7 days, 14 days, 28 days, 60 days, 90 days after the first dose.
Phase I: Anti-human histocompatibility antigen antibody (HLA-Ab) positivity rate	Serum HLA-Ab positivity rate.	Pre-treatment, 28 days, 60 days after the first dose.
Phase I: Serum Interleukin-6 (IL-6) levels	Serum IL-6 levels.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days after the first dose.
Phase I: Serum tumor necrosis factor-α (TNF-α) levels	Serum TNF-α levels.	Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days after the first dose.
Phase II: Adverse event related to CG-BM1 treatment	Any adverse event related to CG-BM1 treatment that occurred during the study period.	From first dose to 180 days after the first dose.
Phase II: Liver transplant-free survival	28-day, 180-day liver transplant-free survival.	28 days, 180 days after the first dose.
Phase II: Changes in Model for end-stage liver disease (MELD) score	MELDScore = 10 * ((0.957 * ln(Creatinine)) + (0.378 * ln(Bilirubin)) + (1.12 * ln(INR))) + 6.43. An increase in the MELD score indicates worse liver function, poorer prognosis, and a higher urgency for liver transplantation.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes in chronic liver failure consortium organ failure score (CLIF-C OFs)	Changes in CLIF-C OFs. Each organ system is scored on a scale to generate the overall CLIF-C OF score, ranging from 0 to 18. The higher the CLIF-C OF score, the poorer the prognosis for the patient, which means a higher short-term mortality rate.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Complication rate	Complication rate within 180 days. Including: cerebral edema, hepatic encephalopathy, infection, hyponatremia, refractory ascites, acute kidney injury, hepatorenal syndrome, hemorrhage, hepatopulmonary syndrome.	180 days after the first dose.
Phase II: Changes of aspartate aminotransferase (AST)	Amount of increase or decrease in serum AST.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of alanine aminotransferase (ALT)	Amount of increase or decrease in serum ALT.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of albumin	Amount of increase or decrease in serum albumin.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of alkaline phosphatase (ALP)	Amount of increase or decrease in serum ALP.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of γ-glutamyl transpeptidase (GGT)	Amount of increase or decrease in serum GGT.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of total bilirubin (TBil)	Amount of increase or decrease in serum TBil.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of international normalized ratio (INR)	Amount of increase or decrease in INR.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes in liver stiffness measurement (LSM) values	Changes in LSM values measured by transient elastography (TE).	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Changes of 15-minute retention rate obtained by indocyanine green (ICG) retention test	Changes of 15-minute retention rate obtained by indocyanine green (ICG) retention test. Inject indocyanine green (ICG) rapidly into a peripheral vein on one side of the patient at a dose of 0.5mg/kg body weight, and start timing immediately after the injection. After 15 minutes, draw 2ml of blood from the opposite side peripheral vein, separate the serum, and measure the concentration of indocyanine green using a spectrophotometer. Calculate the indocyanine green retention rate at 15 minutes using the following formula: ICG Retention Rate (%) = (C15 mg% ÷ 1 mg%) × 100%.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Anti-human histocompatibility antigen antibody (HLA-Ab) positivity rate	Serum HLA-Ab positivity rate.	Pre-treatment, 28 days, 90 days after the first dose.
Phase II: Serum Interleukin-6 (IL-6) levels	Serum IL-6 levels.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Serum tumor necrosis factor-α (TNF-α) levels	Serum TNF-α levels.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.
Phase II: Serum hepatocyte growth factor (HGF) levels	Serum HGF levels.	Pre-treatment, 28 days, 60 days, 90 days, 180 days after the first dose.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou Cellgenes Biotechnology Co.,Ltd

Publications and helpful links

General Publications

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• Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW, George R, Lardo A. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012 Dec 12;308(22):2369-79. doi: 10.1001/jama.2012.25321. Erratum In: JAMA. 2013 Aug 21;310(7):750. George, Richard [added]; Lardo, Albert [added].
• Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, Zheng YB, Gao ZL. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology. 2011 Sep 2;54(3):820-8. doi: 10.1002/hep.24434. Epub 2011 Jul 14.
• Lin BL, Chen JF, Qiu WH, Wang KW, Xie DY, Chen XY, Liu QL, Peng L, Li JG, Mei YY, Weng WZ, Peng YW, Cao HJ, Xie JQ, Xie SB, Xiang AP, Gao ZL. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial. Hepatology. 2017 Jul;66(1):209-219. doi: 10.1002/hep.29189. Epub 2017 May 27.
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• Schacher FC, Martins Pezzi da Silva A, Silla LMDR, Alvares-da-Silva MR. Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial. Can J Gastroenterol Hepatol. 2021 Aug 4;2021:3662776. doi: 10.1155/2021/3662776. eCollection 2021.
• Xu WX, He HL, Pan SW, Chen YL, Zhang ML, Zhu S, Gao ZL, Peng L, Li JG. Combination Treatments of Plasma Exchange and Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Clinical Trial in China. Stem Cells Int. 2019 Feb 4;2019:4130757. doi: 10.1155/2019/4130757. eCollection 2019.
• Li YH, Xu Y, Wu HM, Yang J, Yang LH, Yue-Meng W. Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study. Stem Cell Rev Rep. 2016 Dec;12(6):645-653. doi: 10.1007/s12015-016-9683-3.
• Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N. Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci. 2019 Sep;76(17):3323-3348. doi: 10.1007/s00018-019-03125-1. Epub 2019 May 4.
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• Zhang K, Sun H, Cao H, Jia Y, Shu X, Cao H, Zhang Y, Yang X. The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV-related acute-on-chronic liver failure and liver cirrhosis. Stem Cell Res Ther. 2021 Aug 20;12(1):466. doi: 10.1186/s13287-021-02544-x.
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Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: acute-on-chronic liver failure; bone marrow mesenchymal stem cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: CGBM1-ACLF

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
• product manufactured in and exported from the U.S.: No