Safety Evaluation of MSC-based Therapy for Liver Cihcrosis Treatment

Phase 1Not Yet RecruitingNCT07472270

Vinmec Research Institute of Stem Cell and Gene Technology12 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Liver Cirrhosis

Interventions

Umbilical 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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Frequency and Severity of Adverse Events and Serious Adverse Events

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.

Time frame: 9 months from first infusion

Secondary Outcomes

Blood serum biochemical analysis

Assessment of changes in serum albumin (ALB), AST, ALT, GGT, ALP levels

Time frame: Baseline, day 1, day 30, day 31, day 60, day 61, day 90, day 180, day 270

Child-Pugh score

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).

Time frame: Baseline, day 30, day 60, day 90, day 180, day 270

MELD score

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

Time frame: Baseline, day 30, day 60, day 90, day 180, day 270

Change in quality of life

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.

Time frame: Baseline, day 90, day 180, day 270