A Clinical Trial to Evaluate the Safety, Tolerance and Efficacy of aCell Inj. of Allogeneic UC-MSCs in Patients With Decompensated Hepatitis B Cirrhosis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 主要终点
- Serious Adverse Event (SAE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Human Umbilical Cord Mesenchymal Stem Cells
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
干预措施: Human Umbilical Cord Mesenchymal Stem Cells (Biological)
结局指标
主要结局
Serious Adverse Event (SAE)
时间窗: Through study completion, an average of 1 year
Serious adverse events that occurred during the trial
Dose-limiting toxicity (DLT)
时间窗: Through study completion, an average of 1 year
Dose-limiting toxicity
Adverse Event (AE)
时间窗: Through study completion, an average of 1 year
Adverse events that occurred during the trials
Recommended dose for phase 2 clinical trial (RP2D)
时间窗: Through study completion, an average of 1 year
Recommended dose for phase 2 clinical trial
Maximum Tolerated Dose (MTD)
时间窗: Through study completion, an average of 1 year
Maximum Tolerated Dose
次要结局
- Overall survival(Through study completion, an average of 1 year)
- Eastern Cooperative Oncology Group (ECOG)(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)
- MELD(Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Hepatic stiffness(Day -14 - Day -1, Week 12, Week 20, Week 32, Week 56)
- Child-Pugh(Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Total bilirubin (TBIL)(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)(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)(Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56)
- Helper T cell 17 (Th17)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Alanine aminotransferase (ALT)(Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56)
- Immunoglobulin A (IgA)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Immunoglobulin M (IgM)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Immunoglobulin E (IgE)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Rate of survival(Through study completion, an average of 1 year)
- Alkaline phosphatase (ALP)(Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56)
- Cluster of differentiation 4 (CD4)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Regulatory T cells (Treg)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Carcinoembryonic antigen (CEA)(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)
- Carbohydrate antigen (CA19-9)(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)
- Carbohydrate antigen 15-3 (CA15-3 )(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)
- Aspartate aminotransferase (AST)(Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56)
- Cluster of differentiation 3 (CD3)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Cluster of differentiation 8 (CD8)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Immunoglobulin G (IgG)(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Incidence of liver cancer(Through study completion, an average of 1 year)
- HBV-DNA(Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Albumin (ALB)(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)(Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week 12, Week 20, Week 32, W56)
- Alpha-Fetoprotein-L3 (AFP-13)(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)
- Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA II)(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)
- Incidence of complications associated with decompensated cirrhosis(Through study completion, an average of 1 year)
- Incidence of hepatic failure(Through study completion, an average of 1 year)
- Chronic Liver Disease Questionnaire(Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- EQ-5D-5L(Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- SF-36 Quality of Life Score(Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56)
- Alpha-Fetoprotein (AFP)(Day -14-Day -1, Week 12, Week 20, Week 32, Week 56)