Clinical trial NCT05227846: Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-1)
Official title: A Phase 1 Dose Escalation Study of Human Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Decompensated Cirrhosis (MSC-DLC-1)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Decompensated Cirrhosis
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
Collaborators: name: Vcanbio Cell and Gene Engineering Corp., Ltd.
First posted: 2022-02-07
Enrollment: 12
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 is a Phase 1, open label, dose escalation clinical trial of human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated cirrhosis. The purpose of this study is to assess the safety of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.

Detailed description: 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.

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. Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit.
2. Uncontrolled severe infection within 2 weeks of screening.
3. Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
4. 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.
5. Patients with hepatitis C virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HCV for less than 12 months.
6. Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
7. Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
8. Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
9. Severe jaundice (serum total bilirubin level ≥ 170μmol/L); Significant renal insufficiency (serum creatinine ≥ 1.2 times upper normal limit); Severe electrolyte abnormality (serum sodium level \< 125 mmol/L); Severe leukopenia (white blood cell count \< 1 × 10E9/L).
10. Patients with biliary obstruction, hepatic vein, portal vein, splenic vein thrombosis and portal vein spongiosis.
11. Patients with surgical history such as splenic cut-off flow and portal body shunt.
12. Patients with confirmed or suspected malignancies.
13. Patients with a prior history of major organ transplantation or complicated with significant disease of heart, lung, kidney, blood, endocrine and other systems.
14. Drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
15. HIV seropositivity.
16. Those who have received blood transfusion or other blood products within 1 month prior to screening visit.
17. Pregnancy, lactation or with recent fertility plan.
18. Highly allergic or have a history of severe allergies.
19. Participants in other clinical trials within the last 3 months.
20. Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.

Primary outcomes:
measure: Incidence of Adverse Events Incidence of Adverse Events
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, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months
timeFrame: 3 days, 14 days, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 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: