Clinical trial NCT05984303: Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-1b)
Official title: Treatment of Decompensated Cirrhosis Using Human Umbilical Cord-derived Mesenchymal Stem Cells: A Phase 1, Multiple Administration, Dose-escalasion Trial (MSC-DLC-1b)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Decompensated Cirrhosis
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
Collaborators: name: Wuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd., Hubei, China
First posted: 2023-08-09
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Willing to provide written informed consent;
2. Aged 18 to 75 years (including 18 and 75 years), male or female;
3. 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);
4. Child-Turcotte-Pugh (CTP) score 7 to 12 points.

Exclusion Criteria:

1. 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.
2. 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.
3. Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
4. Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
5. Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
6. Patients with biliary obstruction, or portal patients with vein spongiosis.
7. 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.
8. Patients with history of organ transplantation.
9. Patients with severe heart, lung, kidney and blood system diseases.
10. Patients with drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
11. Patients with history of immunodeficiency disease, including a positive test result for human immunodeficiency virus (HIV) antibodies, or other acquired or congenital immunodeficiency diseases;
12. 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.
13. 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.
14. 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.
15. Patients previously received stem cell therapy or are intolerance to cell therapy;
16. Participants in other clinical trials within the last 3 months.
17. Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: from baseline to 28th day
measure: incidence of dose-limiting toxicity-related adverse events
timeFrame: from baseline to 28th day
measure: maximum tolerated dose
timeFrame: from baseline to 28th day
measure: Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
timeFrame: at 28th day
Secondary outcomes:
measure: 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
timeFrame: 3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months
measure: Incidence of each complication associated with decompensated cirrhosis
timeFrame: up to 24 months
measure: liver transplant-free survival
timeFrame: up to 24 months
measure: Incidence of liver failure
timeFrame: up to 24 months
measure: plasma albumin (ALB)
timeFrame: up to 24 months
measure: plasma prealbumin (PALB)
timeFrame: up to 24 months
measure: total bilirubin (TBIL)
timeFrame: up to 24 months
measure: serum cholinesterase (CHE)
timeFrame: up to 24 months
measure: prothrombin time (PT)
timeFrame: up to 24 months
measure: Child-Turcotte-Pugh (CTP) score
timeFrame: up to 24 months
measure: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
timeFrame: up to 24 months
measure: Incidence of liver cancer
timeFrame: up to 24 months
measure: ChronicLiver Disease Questionnaire (CLDQ)
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing 302 Hospital
Study officials:
affiliation: Beijing 302 Hospital
name: Fu-Sheng Wang, MD, PhD
role: STUDY_CHAIR
References: