Ex Vivo Perfusion of Gene-Edited Porcine Livers in Patients With Severe Hepatic Failure

NCT07519005 | Active Not Recruiting Early Phase 1

• 1 other identifier: KY20252434-C-1
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate whether extracorporeal perfusion using a gene-edited pig liver can significantly improve liver function and serve as a bridge-to-transplant therapy in patients with severe hepatic failure. It will also assess the survival and functionality of the xenogeneic liver and monitor the safety of the procedure. The main questions it aims to answer are:

• Can extracorporeal perfusion with a gene-edited pig liver significantly improve liver function indicators (including biochemical, coagulation, and metabolic parameters) in patients with severe hepatic failure?
• Is the gene-edited pig liver viable and functional during extracorporeal perfusion, as evidenced by bile secretion, adequate blood flow, and acceptable histopathological findings?
• What adverse events occur in participants during and after extracorporeal xenogeneic liver perfusion? This is a single-arm study without a comparison group. Participants will:
• Undergo screening assessments to confirm eligibility for severe hepatic failure diagnosis
• Receive extracorporeal perfusion with a gene-edited pig liver for up to 14 days (or until transplantation/clinical improvement)
• Receive intensive immunosuppressive therapy including tacrolimus, rituximab, ATG, mycophenolate mofetil, and other medications to prevent rejection Undergo hourly vital sign monitoring and daily blood tests (liver function, renal function, coagulation, inflammatory markers) during the perfusion period
• Have daily abdominal ultrasounds and liver biopsies every other day to assess graft function and rejection

Conditions

Hepatic Failure

Outcome Measures

Primary Outcomes (1)

• Change in liver function parameters from baseline

  Evaluation of changes in key liver function biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), and international normalized ratio (INR) measured daily during extracorporeal perfusion. Success is defined as stabilization or improvement of these parameters compared to baseline, indicating the gene-edited porcine liver can effectively support metabolic functions and serve as a bridge-to-transplant therapy.

  From initiation of perfusion (Day 0) until discontinuation of perfusion, up to 14 days

Secondary Outcomes (4)

• Viability and functional capacity of the ex vivo perfused porcine liver

  Daily from Day 0 until graft removal or participant discontinuation, up to 14 days

• Changes in coagulation parameters

  Daily from Day 0 until end of perfusion, up to 14 days

• Inflammatory cytokine levels and immune cell subsets

  Every 2 days from Day 0 until end of perfusion, up to 14 days

• Risk of cross-species viral transmission

  Daily from Day 0 until 7 days after perfusion discontinuation

Study Arms (1)

Ex Vivo Gene-Edited Porcine Liver Perfusion

EXPERIMENTAL

Participants with severe hepatic failure undergo extracorporeal perfusion using a six-gene-edited Bama pig liver. Under local anesthesia, vascular access is established via internal jugular and femoral veins. Immunosuppression includes rituximab (375 mg/m²), ATG (1-1.5 mg/kg/day x 2-3d), tacrolimus (0.01-0.05 mg/kg bid, target 15-25 ng/mL), MMF (1g bid), etanercept (25 mg biweekly), methylprednisolone (20 mg/kg with taper), and eculizumab (900 mg, 24h pre-op). Heparin anticoagulation targets APTT 1.5-2.5x and ACT 200-300s. Perfusion continues until transplantation, recovery, graft failure, or max 14 days, with daily monitoring.

Biological: Ex vivo perfusion of six-gene-edited porcine liver; Drug: Multi-drug immunosuppressive therapy

Interventions

Multi-drug immunosuppressive therapy DRUG

Combination immunosuppression including rituximab, tacrolimus, mycophenolate mofetil, rabbit anti-thymocyte immunoglobulin (ATG), etanercept, methylprednisolone, and eculizumab administered according to a standardized protocol to prevent xenogeneic rejection.

Ex Vivo Gene-Edited Porcine Liver Perfusion

Ex vivo perfusion of six-gene-edited porcine liver BIOLOGICAL

Liver from a six-gene-edited Bama miniature pig (meeting designated pathogen-free standards) perfused extracorporeally using a specialized perfusion platform. The liver is procured using hypothermic preservation (Schüssner's solution and hypertonic citrate-purine solution), transported at 1-6°C, and connected to the patient via internal jugular and femoral venous access. The perfusion maintains physiological temperature and blood flow through the porcine liver while the patient's blood circulates through the graft.

Ex Vivo Gene-Edited Porcine Liver Perfusion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age and Gender: Adults aged 18-70 years, any gender.
• Diagnosis of Severe Hepatic Failure: Patients meeting diagnostic criteria from the "Guidelines for Diagnosis and Treatment of Hepatic Failure (2024 Edition)" including:
• Acute liver failure: Acute onset without underlying liver disease history, developing grade II or higher hepatic encephalopathy within 4 weeks Subacute liver failure: Acute onset without prior liver disease, clinical manifestations of liver failure appearing within 4-24 weeks Acute-on-chronic liver failure: Acute deterioration of liver function on the basis of chronic liver disease (with or without cirrhosis), presenting as liver and/or extrahepatic organ failure with high short-term mortality (28-day mortality ≥15%) Chronic liver failure: Progressive liver function decline on the basis of cirrhosis resulting in chronic hepatic decompensation (recurrent ascites and/or hepatic encephalopathy) All patients must have: Grade II or higher hepatic encephalopathy, confirmed by a third-party independent expert panel of three members assessing poor treatment response and extremely high short-term mortality risk.
• Surgical Tolerance: Other organs besides the liver must be able to tolerate the trauma of extracorporeal liver perfusion surgery.
• Informed Consent: Parents, spouses, and adult children (immediate family members) must be fully informed and voluntarily sign the informed consent form, with ability to complete the trial as required by the protocol.

You may not qualify if:

• Immune Dysfunction: Individuals with HIV infection, diagnosed systemic immune diseases, or those undergoing immunosuppressive therapy affecting systemic immune function.
• Prior Transplantation: Previous recipients of allogeneic tissue or organ transplantation.
• Religious/Ethnic Restrictions: Individuals who cannot accept swine-derived materials due to religious beliefs, ethnic considerations, or other reasons.
• Recent Trial Participation: Participation in other clinical studies within 3 months prior to enrollment.
• Surgical Contraindications: Pathological changes at the planned operative site rendering surgery inoperable, or presence of critical organ failure or systemic severe infections precluding surgical intervention.
• Investigator Discretion: Patients deemed unsuitable for participation by the investigator for other reasons.

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Liver Failure

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Kefeng Dou, Professor

  Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University

  PRINCIPAL INVESTIGATOR

• Kaishan Tao, Professor

  Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University

  PRINCIPAL INVESTIGATOR

• Lin Wang, Professor

  Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single-arm, open-label, prospective study evaluating ex vivo perfusion of gene-edited porcine liver in a patient with severe hepatic failure.

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 9, 2026
• Study Start: January 31, 2026
• Primary Completion: February 3, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)