The Safety and Efficacy of MSC-EVs in Acute/Acute-on-Chronic Liver Failure

NCT05940610 | Withdrawn Phase 1

• 1 other identifier: MSC-EVs-2 of ThirdSunYatSen
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Acute-on-chronic liver failure (ACLF) refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors，while acute liver failure (ALF) refers to a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. Liver transplantation is the only curative treatment for this type of end-stage liver disease, but the rapid disease progression and lack of donors limit its application. The potential of MSCs to repair or regenerate damaged tissue and suppress immune responses makes them promising in the treatment of liver diseases, especially in the field of liver transplantation. Many studies have shown that MSC-based therapies can reduce the symptoms of liver disease due to their paracrine effects. It has been confirmed in previous studies that infusion of allogeneic MSCs is safe and convenient for patients with ACLF and improve liver function and decrease the incidence of severe infections. Compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) are gradually gaining attention for their enhanced safety, as they do not replicate or cause microvascular embolism, and can be easily stored without losing their properties. It represents a novel and effective cell-free therapeutic agent as alternative to cell-based therapies for liver diseases, and liver failure was also concerned. This study was designed to evaluate the safety and efficacy of MSC-EVs in ACLF/ALF .

Conditions

Acute-On-Chronic Liver Failure; Acute Liver Failure

Keywords

MSC-EVs; Acute-on-chronic liver failure; Acute liver failure; Liver transplantation

Outcome Measures

Primary Outcomes (7)

• Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.

  Incidence, timing and severity of any clinical complication related to MSC-EV infusion, such as tympanic body temperature, heart rate, mean arterial blood pressure and allergy, as assessed by CTCAE v4.0 .

  24 hours after injection

• Aspartate aminotransferase (AST)

  Collect clinical results reflecting liver function

  6 months after first rejection

• Alanine aminotransferase (ALT)

  Collect clinical results reflecting liver function

  6 months after first rejection

• Bilirubin level

  Collect clinical results reflecting liver function

  6 months after first rejection

• International normalized ratio (INR)

  Collect clinical results reflecting liver function

  6 months after first rejection

• Carbohydrate Compound antigen (GGT) level

  Collect clinical results reflecting liver function

  6 months after first rejection

• Adverse events

  Any adverse events which may related to MSC-EV infusion

  6 months after first rejection

Secondary Outcomes (2)

• Number of survived patients at 1 year, according to the follow-up results

  12 months

• Proportion of immune cell subsets from biopsy or blood samples ,at months 1-6 after infusion.

  6 months

Study Arms (2)

MSC-EV group

EXPERIMENTAL

On the basis of standard medical treatment, an additional injection of MSC-EVs will be received by participants once a week for 4 weeks while hospitalized.

Biological: MSC-EVs

Non-MSC-EV group

NO INTERVENTION

In the non-MSC-EV group, patients will receive standard medical treatment and 100ml saline as a control.

Interventions

MSC-EVs BIOLOGICAL

10 E10 MSC-EV particles per 100ml for a single dose. Once a week for 4 weeks.

MSC-EV group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 18-65 years old;
• Acute on chronic liver failure-which is characterized by acute hepatic insult manifesting as jaundice (serum total bilirubin \[TBil\] ≥ 10×ULN umol/L) and coagulopathy (international normalized ratio \[INR\] ≥ 1.5 or prothrombin activity \< 40%), complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination, in patients with previously diagnosed or undiagnosed chronic liver disease; Acute liver failure-a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease.
• Total bilirubin (TBil) ≥ 171umolL or daily increase ≥17.1umol/L;
• Prothrombin activity (PTA) between 20% and 40% (or INR between 1.5 and 2.6);
• No hepatic encephalopathy, or encephalopathy below grade II (including grade II);

You may not qualify if:

• Patients with primary or metastatic liver cancer
• Severe active bleeding or diffuse intravascular coagulation
• Patients who are allergic to blood products or drugs used in treatment, such as plasma, heparin and protamine;
• MELD score \>30
• Other serious disease including heart disease, lung disease, blood disease, autoimmune disease, diabetes, active uncontrolled infection,etc.

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

Third Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510630, China

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure; Liver Failure, Acute

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University

Study Record Dates

• First Submitted: July 2, 2023
• First Posted: July 11, 2023
• Study Start: September 1, 2023
• Primary Completion: September 30, 2024
• Study Completion: October 1, 2025
• Last Updated: October 12, 2023

Record last verified: 2023-10

Locations

CN (1)