Decompensated Liver CirrhosisPhase 1/2NCT05948982
Safety of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in Patients With Decompensated Hepatitis B Cirrhosis
A Phase 1/2 study testing Human Umbilical Cord Mesenchymal Stem Cells in people with Decompensated Liver Cirrhosis, run by Asia Cell Therapeutics (Shanghai) Co., Ltd..
Trial summary
The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses of human umbilical cord mesenchymal stem cell injection in patients with decompensated hepatitis B cirrhosis, and to further explore the efficacy, pharmacodynamic profile and appropriate dose of administration to provide a… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Decompensated Liver Cirrhosis
- What is being tested?
- Human Umbilical Cord Mesenchymal Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 30 Jul 2023to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 75 years old (including borderline values) at screening, regardless of gender
- Diagnosed with decompensated hepatitis B cirrhosis according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 edition)
- There's no significant reduction in cirrhotic symptoms or no significant improvement in quality of life score after more than 3 months of strict medical conservative treatment
- HBV DNA ≤ 1000 IU/mL at the time of screening
- Fully understand the informed consent form, voluntarily subject to the trial and sign the informed consent form.
Who cannot join
- other causes of cirrhosis, such as alcoholic hepatitis, viral hepatitis C, autoimmune hepatitis and metabolic-related fatty liver disease
- Child-Pugh score >12;
- History of malignancy of the liver or other organs, or a family history of liver malignancy in three generations of immediate family members;
- Current serious medical conditions that would affect your safety and treatment efficacy assessment as determined by the investigator, such as: Class II or higher abnormal cardiac function (NYHA criteria), cardiovascular disease such as ischemic heart disease (e.g., myocardial infarction or angina), poorly controlled diabetes (fasting glucose ≥ 10 mmol/L or glycated hemoglobin (HbA1c) ≥ 8%), serum creatinine > 2 times the upper limit of normal (ULN), etc;
- Recent uncontrolled gastrointestinal bleeding (e.g., severe bleeding tendency or active bleeding within 3 months prior to screening, or clinically significant upper gastrointestinal hemorrhage event within 4 weeks prior to screening), as determined by the investigator to be unsuitable for participation in this trial;
- Have had hepatic encephalopathy or hepatorenal syndrome within 3 months prior to screening
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- Spontaneous peritonitis or a more severe active infection within 2 weeks prior to the trial
- Positive infectious disease test (serum anti-HIV antibody, anti-HCV antibody, syphilis antibody either positive) or active tuberculosis;
- Those who have received human albumin within 3 weeks prior to the first infusion of the test drug;
- Those who have the history of venous thrombosis or pulmonary embolism
- Drug addicted or alcohol abusers;
- Women who are pregnant or breastfeeding;
- Persons with a history of severe drug allergy or hypersensitivity;
- History of a serious mental disorder, including uncontrolled major depression or controlled or uncontrolled psychosis, within 24 months prior to screening;
- Those who have participated in other interventional clinical trials within 3 months prior to screening or are participating in other interventional clinical trials, or who have received prior stem cell therapy
- Those who are proposed for liver transplantation within 3 months;
- Other conditions that, in the opinion of the investigator, are not suitable for participation in this clinical trial.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Clinical Trial to Evaluate the Safety, Tolerance and Efficacy of aCell Inj. of Allogeneic UC-MSCs in Patients With Decompensated Hepatitis B Cirrhosis
The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses of human umbilical cord mesenchymal stem cell injection in patients with decompensated hepatitis B cirrhosis, and to further explore the efficacy, pharmacodynamic profile and appropriate dose of administration to provide a basis for the use of safer and more effective treatments for patients with decompensated hepatitis B cirrhosis in the future.
Participants are required to sign an informed consent form and, after undergoing a series of tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group for intravenous infusion of human umbilical cord mesenchymal stem cells.
Read the detailed description
Cirrhosis decompensated stage is an advanced stage of liver disease caused by various chronic liver damages, and 77% of cirrhosis patients in China are caused by hepatitis B virus (HBV). The current treatment for patients with cirrhotic decompensation is mainly symptomatic treatment with drugs targeting the cause, anti-liver fibrosis drugs and supplemental albumin, diuresis, endoscopic sclerosis or ligation, blood purification (artificial liver) and vascular intervention. Although these treatments are effective in slowing down the progression of the disease in patients, they cannot completely reverse the decompensation of liver function in all patients. Currently, liver transplantation remains the most effective treatment for decompensated cirrhosis. However, due to the lack of donor liver sources, only a small number of patients can be treated with transplantation.
In recent years, with the in-depth research in the field of stem cells and regenerative medicine, the therapeutic role of stem cells in end-stage liver disease has received increasing attention based on their biological functions such as tissue damage repair and immune regulation. A large number of clinical exploratory studies on stem cell transplantation for liver diseases have been conducted by scholars in the field, and the published findings suggest that MSC transplantation can improve the liver function index of patients, and the appetite, mental and physical strength of patients improved significantly after infusion.
The investigators hope that the final research results will provide safe, effective and more accessible treatments for more patients in the same category, improve their quality of life and fill the gap in the field of regenerative medicine for the treatment of hepatitis B cirrhosis in the decompensated stage.
The main objective of this study was to evaluate the safety and tolerability of multiple doses of human umbilical cord MSC injection in patients with decompensated hepatitis B cirrhosis, and to further explore the efficacy, pharmacodynamic characteristics and appropriate doses for future use of safer and more effective treatments for patients with decompensated hepatitis B cirrhosis.
The test drug used in this study is called Human Umbilical Cord Mesenchymal Stem Cell Injection, and this study drug is not yet approved for marketing. This product is 10 ml, 1×100000000 cells, packaged in a cell lyophilization bag, and manufactured and supplied by Asia Cell Therapeutics (Shanghai) Co., Ltd.. The excipients of this product include dimethyl sulfoxide (DMSO), human blood albumin (HSA) and compound electrolyte injection. Quality control tests showed that the survival rate of recovered cells after lyophilization was not less than 80% within 6 hours. The cell sterility check, mycoplasma, specific human-derived virus, surface antigen and tumorigenicity were all negative. All quality control results met the requirements of the 2020 version of the Chinese Pharmacopoeia or related testing standards.
Non-clinical and other clinical studies suggest that human umbilical cord MSCs can alter the tissue microenvironment through paracrine mechanisms, provide nutrients and an environment conducive to liver proliferation and repair, promote damaged liver regeneration and liver vascular regeneration, inhibit the proliferation and migration of immune cells to the liver, regulate liver and systemic immune inflammatory responses, thereby reducing liver damage and inhibiting the formation of liver fibrosis. In addition, human umbilical cord MSCs may have the potential to differentiate into hepatocytes (a type of cell with normal hepatocyte function), thereby replenishing damaged liver tissue and improving liver function.
The human umbilical cord MSC injections used in this study have been studied by the National Health Care Commission (NHC)/Central Military Commission (CMC) General Directorate of Health (GMDH) and have accumulated a certain amount of human safety and efficacy data in patients with inhalation lung injury, burn injury and decompensated hepatitis B cirrhosis.
This study was a multiple-dose, open, dose-escalation design. Subjects enrolled in this study will enter the low (1 x 1000000 cells/kg), medium (2 x 1000000 cells/kg), and high (4 x 1000000 cells/kg) dose groups on a sequential entry basis, with each subject receiving only one corresponding dose. The infusion route of human umbilical cord MSC injection is the peripheral vein, and the frequency of treatment is one infusion every 4 weeks, for a total of three infusions, and the subjects will be hospitalized at the study center for 3-7 days after each infusion (the exact duration can be determined by the investigator on a case-by-case basis).
Dosing regimen:
The titration will be completed within 6 hours after the cell preparation has been resuscitated and prepared, the infusion will take no less than 45 minutes, and participants will be closely observed for at least 2 hours after the infusion.
After the first subject in the same dose group has completed 14 days of safety observation after the first dose, the second to sixth subjects in that group may begin dosing on a case-by-case basis, with a minimum of 3 days between enrollment in the high dose group, with the specific interval being adjusted based on the safety data that have been generated. The first subject in the next dose group may be started 28 days after the last subject in the previous dose group completes the first dose. During the dose escalation process, the investigator and sponsor will determine whether to proceed to the next dose group based on the safety data from the previous dose group.
- Conditions
- Decompensated Liver Cirrhosis
- Being tested
- Human Umbilical Cord Mesenchymal Stem Cells
- Keywords
- Decompensated hepatitis B cirrhosis, Human Umbilical Cord Mesenchymal Stem Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Umbilical Cord Mesenchymal Stem CellsBiological
The stem cell infusion route is peripheral intravenous infusion, once every 4 weeks for a total of 3 infusions. All subjects received experimental drugs and conventional treatment during the study period.
| Study group | Role | What they receive |
|---|---|---|
| Human Umbilical Cord Mesenchymal Stem Cells | Experimental | The trial was divided into three dose groups： Low-dose group: 1000000 cells/kg Medium-dose group: 2000000 cells/kg High-does group: 4000000 cells/kg Receives: Biological: Human Umbilical Cord Mesenchymal Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Event (AE)
Adverse events that occurred during the trials
Measured: Through study completion, an average of 1 year
Serious Adverse Event (SAE)
Serious adverse events that occurred during the trial
Measured: Through study completion, an average of 1 year
Recommended dose for phase 2 clinical trial (RP2D)
Recommended dose for phase 2 clinical trial
Measured: Through study completion, an average of 1 year
Dose-limiting toxicity (DLT)
Dose-limiting toxicity
Measured: Through study completion, an average of 1 year
Maximum Tolerated Dose (MTD)
Maximum Tolerated Dose
Measured: Through study completion, an average of 1 year
Secondary outcomes (36)
Overall survival
Time of survival
Measured: Through study completion, an average of 1 year
Rate of survival
Rate of survival without liver transplantation
Measured: Through study completion, an average of 1 year
Child-Pugh
The Child-Pugh score included a score for five indicators: hepatic encephalopathy, ascites, total bilirubin concentration, albumin concentration, and prothrombin time extension. For each indicator, the lowest score is 1, the highest score is 3, and the total score of each indicator is calculated. A higher score indicates more severe disease.
Measured: Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
MELD
The Model for End-stage Liver Disease is a scoring system based on serum creatinine, international standardized ratio, total bilirubin combined with the cause of cirrhosis to evaluate the liver function reserve and prognosis of patients with chronic liver disease. Calculating formula for R = 3.78 * ln [T - Bil (umol/L) / 17.1] ln (INR) + 9.57 + 11.2 * * ln Cr (umol/L) / 88.4 + 6.43 * the etiology.
(Etiology: 0 for cholestatic cirrhosis and alcoholic cirrhosis, 1 for viral and other causes)
Measured: Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Hepatic stiffness
Based on transient elastography fibroscan, observe the liver stiffness.
Measured: Day -14 - Day -1, Week 12, Week 20, Week 32, Week 56
Alanine aminotransferase (ALT)
The concentration of ALT
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Aspartate aminotransferase (AST)
The concentration of AST
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Total bilirubin (TBIL)
The concentration of TBIL
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
γ-glutamyl transpeptidase (γ-GT)
The concentration of γ-GT
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Alkaline phosphatase (ALP)
The concentration of ALP
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Albumin (ALB)
The concentration of ALB
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Cholinesterase (CHE)
The concentration of CHE
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
International Normalized Ratio (INR)
INR was calculated by the PT ratio of the reference plasma measured by thrombin to normal plasma and the ISI value marked by the reagent used. The higher the INR, the longer it takes for blood to clot
Measured: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week 12, Week 20, Week 32, W56
Cluster of differentiation 3 (CD3)
The concentration of CD3
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Cluster of differentiation 4 (CD4)
The concentration of CD4
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Cluster of differentiation 8 (CD8)
The concentration of CD8
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Regulatory T cells (Treg)
The concentration of Treg
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Helper T cell 17 (Th17)
The concentration of Th17
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin A (IgA)
The concentration of IgA
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin G (IgG)
The concentration of IgG
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin M (IgM)
The concentration of IgM
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin E (IgE)
The concentration of IgE
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Alpha-Fetoprotein (AFP)
The concentration of AFP
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Alpha-Fetoprotein-L3 (AFP-13)
The concentration of AFP-L3
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Carcinoembryonic antigen (CEA)
The concentration of CEA
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Carbohydrate antigen (CA19-9)
The concentration of CA19-9
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Carbohydrate antigen 15-3 (CA15-3 )
The concentration of CA15-3
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA II)
The concentration of PIVKA II
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Incidence of liver cancer
Calculate the number of subjects who developed liver cancer during the trial after drug administration as a percentage of all subjects
Measured: Through study completion, an average of 1 year
HBV-DNA
The concentration of HBV-DNA
Measured: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Eastern Cooperative Oncology Group (ECOG)
The ECOG score is an indicator of a patient's general health and ability to tolerate treatment from their physical strength. The ECOG physical condition scoring standard scores 0-5 points. The higher the score is, the worse the physical condition of patient is.
Measured: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Incidence of complications associated with decompensated cirrhosis
Diagnosis and severity assessment of complications
Measured: Through study completion, an average of 1 year
Incidence of hepatic failure
Proportion of subjects who developed liver failure
Measured: Through study completion, an average of 1 year
SF-36 Quality of Life Score
The 36-item Short-Form Health Questionnaire (SF-36) is a universal measurement scale developed by the Medical Outcomes Study (MOS) in the United States. It consists of 36 entries covering eight areas: physical function, physical role, physical pain, general health, vitality, social function, emotional role, and mental health. Each section is scored from 0 to 100 points. The score directly reflects the quality of health, the higher the score, the better the function of this aspect, the higher the quality of life.
Measured: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Chronic Liver Disease Questionnaire
The Chronic Liver Disease questionnaire was designed to measure the overall body feeling of the participants within the last two weeks. The total score of the questionnaire ranges from 29 points to 203 points, and the lower the score, the worse the physical condition
Measured: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
EQ-5D-5L
Health questionnaire about subjects' condition.
Measured: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2023
- Study start30 Jul 2023 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Decompensated Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asia Cell Therapeutics (Shanghai) Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lungen Lu, MD, Principal investigator, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05948982
- Sponsor's protocol ID
- QS-UCMSC-DLC
- Status last verified
- Jul 2023
- First submitted
- 25 May 2023
- Last updated
- 17 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial to Evaluate the Safety, Tolerance and Efficacy of aCell Inj. of Allogeneic UC-MSCs in Patients With Decompensated Hepatitis B Cirrhosis
- ClinicalTrials.gov ID
- NCT05948982
- Acronym / sponsor ID
- QS-UCMSC-DLC
- Conditions
- Decompensated Liver Cirrhosis
- Keywords
- Decompensated hepatitis B cirrhosis, Human Umbilical Cord Mesenchymal Stem Cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Asia Cell Therapeutics (Shanghai) Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 30 Jul 2023 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 17 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses of human umbilical cord mesenchymal stem cell injection in patients with decompensated hepatitis B cirrhosis, and to further explore the efficacy, pharmacodynamic profile and appropriate dose of administration to provide a basis for the use of safer and more effective treatments for patients with decompensated hepatitis B cirrhosis in the future.
Participants are required to sign an informed consent form and, after undergoing a series of tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group for intravenous infusion of human umbilical cord mesenchymal stem cells.
Detailed description
Cirrhosis decompensated stage is an advanced stage of liver disease caused by various chronic liver damages, and 77% of cirrhosis patients in China are caused by hepatitis B virus (HBV). The current treatment for patients with cirrhotic decompensation is mainly symptomatic treatment with drugs targeting the cause, anti-liver fibrosis drugs and supplemental albumin, diuresis, endoscopic sclerosis or ligation, blood purification (artificial liver) and vascular intervention. Although these treatments are effective in slowing down the progression of the disease in patients, they cannot completely reverse the decompensation of liver function in all patients. Currently, liver transplantation remains the most effective treatment for decompensated cirrhosis. However, due to the lack of donor liver sources, only a small number of patients can be treated with transplantation.
In recent years, with the in-depth research in the field of stem cells and regenerative medicine, the therapeutic role of stem cells in end-stage liver disease has received increasing attention based on their biological functions such as tissue damage repair and immune regulation. A large number of clinical exploratory studies on stem cell transplantation for liver diseases have been conducted by scholars in the field, and the published findings suggest that MSC transplantation can improve the liver function index of patients, and the appetite, mental and physical strength of patients improved significantly after infusion.
The investigators hope that the final research results will provide safe, effective and more accessible treatments for more patients in the same category, improve their quality of life and fill the gap in the field of regenerative medicine for the treatment of hepatitis B cirrhosis in the decompensated stage.
The main objective of this study was to evaluate the safety and tolerability of multiple doses of human umbilical cord MSC injection in patients with decompensated hepatitis B cirrhosis, and to further explore the efficacy, pharmacodynamic characteristics and appropriate doses for future use of safer and more effective treatments for patients with decompensated hepatitis B cirrhosis.
The test drug used in this study is called Human Umbilical Cord Mesenchymal Stem Cell Injection, and this study drug is not yet approved for marketing. This product is 10 ml, 1×100000000 cells, packaged in a cell lyophilization bag, and manufactured and supplied by Asia Cell Therapeutics (Shanghai) Co., Ltd.. The excipients of this product include dimethyl sulfoxide (DMSO), human blood albumin (HSA) and compound electrolyte injection. Quality control tests showed that the survival rate of recovered cells after lyophilization was not less than 80% within 6 hours. The cell sterility check, mycoplasma, specific human-derived virus, surface antigen and tumorigenicity were all negative. All quality control results met the requirements of the 2020 version of the Chinese Pharmacopoeia or related testing standards.
Non-clinical and other clinical studies suggest that human umbilical cord MSCs can alter the tissue microenvironment through paracrine mechanisms, provide nutrients and an environment conducive to liver proliferation and repair, promote damaged liver regeneration and liver vascular regeneration, inhibit the proliferation and migration of immune cells to the liver, regulate liver and systemic immune inflammatory responses, thereby reducing liver damage and inhibiting the formation of liver fibrosis. In addition, human umbilical cord MSCs may have the potential to differentiate into hepatocytes (a type of cell with normal hepatocyte function), thereby replenishing damaged liver tissue and improving liver function.
The human umbilical cord MSC injections used in this study have been studied by the National Health Care Commission (NHC)/Central Military Commission (CMC) General Directorate of Health (GMDH) and have accumulated a certain amount of human safety and efficacy data in patients with inhalation lung injury, burn injury and decompensated hepatitis B cirrhosis.
This study was a multiple-dose, open, dose-escalation design. Subjects enrolled in this study will enter the low (1 x 1000000 cells/kg), medium (2 x 1000000 cells/kg), and high (4 x 1000000 cells/kg) dose groups on a sequential entry basis, with each subject receiving only one corresponding dose. The infusion route of human umbilical cord MSC injection is the peripheral vein, and the frequency of treatment is one infusion every 4 weeks, for a total of three infusions, and the subjects will be hospitalized at the study center for 3-7 days after each infusion (the exact duration can be determined by the investigator on a case-by-case basis).
Dosing regimen:
The titration will be completed within 6 hours after the cell preparation has been resuscitated and prepared, the infusion will take no less than 45 minutes, and participants will be closely observed for at least 2 hours after the infusion.
After the first subject in the same dose group has completed 14 days of safety observation after the first dose, the second to sixth subjects in that group may begin dosing on a case-by-case basis, with a minimum of 3 days between enrollment in the high dose group, with the specific interval being adjusted based on the safety data that have been generated. The first subject in the next dose group may be started 28 days after the last subject in the previous dose group completes the first dose. During the dose escalation process, the investigator and sponsor will determine whether to proceed to the next dose group based on the safety data from the previous dose group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Human Umbilical Cord Mesenchymal Stem Cells | Experimental | Biological: Human Umbilical Cord Mesenchymal Stem CellsThe trial was divided into three dose groups： Low-dose group: 1000000 cells/kg Medium-dose group: 2000000 cells/kg High-does group: 4000000 cells/kg |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18 to 75 years old (including borderline values) at screening, regardless of gender
- Diagnosed with decompensated hepatitis B cirrhosis according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 edition)
- There's no significant reduction in cirrhotic symptoms or no significant improvement in quality of life score after more than 3 months of strict medical conservative treatment
- HBV DNA ≤ 1000 IU/mL at the time of screening
- Fully understand the informed consent form, voluntarily subject to the trial and sign the informed consent form.
Key exclusion criteria (17 listed)
- other causes of cirrhosis, such as alcoholic hepatitis, viral hepatitis C, autoimmune hepatitis and metabolic-related fatty liver disease
- Child-Pugh score >12;
- History of malignancy of the liver or other organs, or a family history of liver malignancy in three generations of immediate family members;
- Current serious medical conditions that would affect your safety and treatment efficacy assessment as determined by the investigator, such as: Class II or higher abnormal cardiac function (NYHA criteria), cardiovascular disease such as ischemic heart disease (e.g., myocardial infarction or angina), poorly controlled diabetes (fasting glucose ≥ 10 mmol/L or glycated hemoglobin (HbA1c) ≥ 8%), serum creatinine > 2 times the upper limit of normal (ULN), etc;
- Recent uncontrolled gastrointestinal bleeding (e.g., severe bleeding tendency or active bleeding within 3 months prior to screening, or clinically significant upper gastrointestinal hemorrhage event within 4 weeks prior to screening), as determined by the investigator to be unsuitable for participation in this trial;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human Umbilical Cord Mesenchymal Stem CellsThe stem cell infusion route is peripheral intravenous infusion, once every 4 weeks for a total of 3 infusions. All subjects received experimental drugs and conventional treatment during the study period. | Biological | Human Umbilical Cord Mesenchymal Stem Cells |
Primary outcome
Adverse Event (AE)
Time frame: Through study completion, an average of 1 year
Adverse events that occurred during the trials
Serious Adverse Event (SAE)
Time frame: Through study completion, an average of 1 year
Serious adverse events that occurred during the trial
Recommended dose for phase 2 clinical trial (RP2D)
Time frame: Through study completion, an average of 1 year
Recommended dose for phase 2 clinical trial
Dose-limiting toxicity (DLT)
Time frame: Through study completion, an average of 1 year
Dose-limiting toxicity
Maximum Tolerated Dose (MTD)
Time frame: Through study completion, an average of 1 year
Maximum Tolerated Dose
36 secondary outcomes
Overall survival
Time frame: Through study completion, an average of 1 year
Rate of survival
Time frame: Through study completion, an average of 1 year
Child-Pugh
Time frame: Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
MELD
Time frame: Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Hepatic stiffness
Time frame: Day -14 - Day -1, Week 12, Week 20, Week 32, Week 56
Alanine aminotransferase (ALT)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Aspartate aminotransferase (AST)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Total bilirubin (TBIL)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
γ-glutamyl transpeptidase (γ-GT)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Alkaline phosphatase (ALP)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Albumin (ALB)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
Cholinesterase (CHE)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56
International Normalized Ratio (INR)
Time frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week 12, Week 20, Week 32, W56
Cluster of differentiation 3 (CD3)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Cluster of differentiation 4 (CD4)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Cluster of differentiation 8 (CD8)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Regulatory T cells (Treg)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Helper T cell 17 (Th17)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin A (IgA)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin G (IgG)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin M (IgM)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Immunoglobulin E (IgE)
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Alpha-Fetoprotein (AFP)
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Alpha-Fetoprotein-L3 (AFP-13)
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Carcinoembryonic antigen (CEA)
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Carbohydrate antigen (CA19-9)
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Carbohydrate antigen 15-3 (CA15-3 )
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA II)
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Incidence of liver cancer
Time frame: Through study completion, an average of 1 year
HBV-DNA
Time frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Eastern Cooperative Oncology Group (ECOG)
Time frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56
Incidence of complications associated with decompensated cirrhosis
Time frame: Through study completion, an average of 1 year
Incidence of hepatic failure
Time frame: Through study completion, an average of 1 year
SF-36 Quality of Life Score
Time frame: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Chronic Liver Disease Questionnaire
Time frame: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
EQ-5D-5L
Time frame: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lungen Lu, MD principal investigator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Human Umbilical Cord Mesenchymal Stem Cells in people with Decompensated Liver Cirrhosis, run by Asia Cell Therapeutics (Shanghai) Co., Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wenli Liu (+86 13402137712, liuwenli@xibaozhiliao.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Event (AE) (time frame: Through study completion, an average of 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2023.