Treatment of Decompensated Cirrhosis Using Human Umbilical Cord-derived Mesenchymal Stem Cells: A Phase 1, Multiple Administration, Dose-escalasion Trial (MSC-DLC-1b)
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
This clinical trial is a Phase 1, multiple administration, dose-escalasion clinical trial of human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated cirrhosis. The primary objective of this study is to assess the safety of intravenous infusion of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.
详细描述
Decompensated cirrhosis has a high overall mortality rate. There is unmet need for safe and alternative therapeutic potions. This clinical trial is a Phase 1, multiple administration, dose-escalasion clinical trial of human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated cirrhosis. The primary objective of this study is to assess the safety of intravenous infusion of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.In order to illustrate the safety and effectiveness of human umbilical cord-derived mesenchymal stem cells and the patient's dose tolerance to human umbilical cord-derived mesenchymal stem cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Willing to provide written informed consent;
- •Aged 18 to 75 years (including 18 and 75 years), male or female;
- •Patients diagnosed with decompensated liver cirrhosis based on clinical findings, laboratory tests, imaging findings and/or representative pathological findings (decompensated liver cirrhosis is defined as the occurrence of at least one serious complication, including esophageal and gastric varices bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis and other serious complications);
- •Child-Turcotte-Pugh (CTP) score 7 to 12 points.
排除标准
- •Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening, or patients with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HBV for less than 12 months.
- •Hepatitis C virus (HCV) RNA ≥ detection limit at the time of screening, or patients with hepatitis C virus-related decompensated liver cirrhosis not more than 12 months on antiviral therapy.
- •Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
- •Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
- •Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
- •Patients with biliary obstruction, or portal patients with vein spongiosis.
- •Patients are known with other malignancies within 5 years prior to the signing of ICF, except have had curative therapy of Basal Cell Cancer, Squamous Cell Carcinoma and/or radical resection of Carcinoma in Situ.
- •Known to have had other malignancies within 5 years prior to signing the informed consent, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ with curable resection.
- •Patients with history of organ transplantation.
- •Patients with severe heart, lung, kidney and blood system diseases.
- •Patients with drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
- •Patients with history of immunodeficiency disease, including a positive test result for human immunodeficiency virus (HIV) antibodies, or other acquired or congenital immunodeficiency diseases;
- •Pregnant or lactating female. Fertile patients who were unable or unwilling to use effective non-pharmaceutical contraception during the trial and within 6 months after the end of the trial.
- •Patients who had cardiovascular and cerebrovascular events (such as Unstable Angina, Brain Hemorrhage, severe Ischemic Infarction) within 3 months before the first dose；Patients who had Myocardial Infarct or a clinically significant Arrhythmia/Conduction Abnormalities within 12 months before the first dose.
- •Patients with hypersensitivity (allergic to more than two foods or drugs) or with a history of severe allergy, or patients with Severe allergy to a known experimental drug or to any excipient.
- •Patients previously received stem cell therapy or are intolerance to cell therapy;
- •Participants in other clinical trials within the last 3 months.
- •Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.
研究组 & 干预措施
Human Umbilical Cord-derived Mesenchymal Stem Cells
Standard of care (SOC) plus a multiple administration and dose-escalasion with 2 cohorts with 3 subjects/cohort who receive doses of 1 and 2 ×10E8 cells. Each person received 3 infusions, 1 week apart, Proceed from lower dose to higher dose if no safety concerns for each cohort.
干预措施: Human Umbilical Cord-derived Mesenchymal Stem Cells (Biological)
结局指标
主要结局
Incidence of Adverse Events
时间窗: from baseline to 28th day
incidence of dose-limiting toxicity-related adverse events
时间窗: from baseline to 28th day
maximum tolerated dose
时间窗: from baseline to 28th day
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
时间窗: at 28th day
The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology. The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).
次要结局
- serum cholinesterase (CHE)(up to 24 months)
- prothrombin time (PT)(up to 24 months)
- plasma albumin (ALB)(up to 24 months)
- total bilirubin (TBIL)(up to 24 months)
- liver transplant-free survival(up to 24 months)
- Change in Model for End-Stage Liver Disease (MELD) score from baseline to 3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months(3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months)
- Incidence of each complication associated with decompensated cirrhosis(up to 24 months)
- EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)(up to 24 months)
- ChronicLiver Disease Questionnaire (CLDQ)(up to 24 months)
- Incidence of liver failure(up to 24 months)
- plasma prealbumin (PALB)(up to 24 months)
- Child-Turcotte-Pugh (CTP) score(up to 24 months)
- Incidence of liver cancer(up to 24 months)
研究者
Fu-Sheng Wang
Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor
Beijing 302 Hospital