Liver Cirrhosis
Conditions
Brief summary
This study Phase 1 clinical trial aimed to evaluate the safety and preliminary efficacy of intravenously administered extracellular vesicles derived from umbilical cord mesenchymal stem cells (UC-MSC-EVs; VinEV-3) in patients with liver cirrhosis. The trial uses a rolling six dose-escalation design, enrolling up to 12 adult patients (18-75 years) with Child-Pugh scores of 7-12. The results of this study are expected to provide initial clinical evidence supporting the safety and potential therapeutic role of UC-MSC-EVs as a novel cell-free treatment approach for liver cirrhosis.
Interventions
BIOLOGICALUmbilical cord mesenchymal stem cell-derived extracellular vesicles
Dimedrol 20 mg will be administered intravenously 15-30 minutes prior to EV infusion. VinEV-3 will be administered at a starting dose of 2 × 10¹⁰ EV particles/kg, with dose escalation to 4 × 10¹⁰ EV particles/kg in the absence of dose-limiting toxicity or dose reduction to 1 × 10¹⁰ EV particles/kg if dose-limiting toxicity occurs. Three infusions will be given at 30 ± 5 day intervals, 3 times, with safety follow-up through 9 months after the first infusion
Sponsors
Vinmec Research Institute of Stem Cell and Gene Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Intervention therapy: VinEV-3 (MSC-derived extracellular vesicles) * Premedication: diphenhydramine (Dimedrol) 20 mg i.v., 15-30 minutes before EV infusion * Route: intravenous * Dose levels: * Starting dose: 2 × 10¹⁰ EV particles/kg * Higher dose: 4 × 10¹⁰ EV particles/kg * Dose reduction to 1 × 10¹⁰ EV particles/kg in case of dose-limiting toxicity * Infusion volume: 100 mL (VinEV-3 diluted in 0.9% sodium chloride) * Infusion duration: \ 60 minutes (\ 1.67 mL/min) * Administration: 3 infusions, 30 ± 5 days apart * Follow-up: 3, 6, and 9 months after first infusion * Concomitant therapy: standard of care, including antiviral therapy for hepatitis B when applicable
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Liver cirrhosis due to alcohol-related liver disease or chronic hepatitis B or C * Child-Pugh score 7-12 * Alcohol-related cirrhosis: abstinent from alcohol ≥ 3 months * HBV/HCV-related cirrhosis: viral disease controlled according to standard clinical criteria * Written informed consent provided
Exclusion criteria
* Significant renal dysfunction or coagulation abnormalities * Liver cirrhosis of unknown etiology * Current or suspected hepatocellular carcinoma or history of malignancy * Portal vein thrombosis * Pregnancy, breastfeeding, or inadequate contraception * Severe renal, respiratory, cardiovascular, infectious, autoimmune, metabolic, or neurological disorders that may interfere with study participation * Refractory ascites at screening * Use of known hepatotoxic medications within a clinically relevant period * Coinfection with HIV, tuberculosis, or other causes of chronic liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Adverse Events and Serious Adverse Events | 9 months from first infusion | Incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0 and dose-limiting toxicities (DLTs) when administered VinEV-3 at escalating dose levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood serum biochemical analysis | Baseline, day 1, day 30, day 31, day 60, day 61, day 90, day 180, day 270 | Assessment of changes in serum albumin (ALB), AST, ALT, GGT, ALP levels |
| Child-Pugh score | Baseline, day 30, day 60, day 90, day 180, day 270 | The Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis. It consists of five clinical measures: total bilirubin, serum albumin, prothrombin time (INR), ascites, and hepatic encephalopathy. The total score ranges from 5 to 15, where higher scores indicate worse hepatic impairment (Class A: 5-6 points, Class B: 7-9 points, and Class C: 10-15 points). |
| MELD score | Baseline, day 30, day 60, day 90, day 180, day 270 | The Model for End-Stage Liver Disease (MELD) is a scoring system used to estimate the severity of chronic liver disease. The score is calculated using a formula that includes serum bilirubin, serum creatinine, and the international normalized ratio (INR). MELD scores range from 6 to 40, where a higher score indicates a more severe disease state and a higher risk of mortality |
| Change in quality of life | Baseline, day 90, day 180, day 270 | Quality of life will be assessed using the Short Form-36 (SF-36) Health Survey. The survey consists of 36 questions covering 8 health domains. Each domain is scored on a scale of 0 to 100, where higher scores indicate a better quality of life and better health status. |
Countries
Vietnam
Contacts
CONTACTThanh Liem Nguyen
CONTACTVan T. Hoang
PRINCIPAL_INVESTIGATORThanh Liem Nguyen
Vinmec Research Institute of Stem Cell and Gene Technology Hanoi, Vietnam 100000
Outcome results
None listed