Acute on Chronic Liver Failure (ACLF), Hepatic Encephalopathy (HE)
Conditions
Keywords
Extra-corporeal live cross-circulation, Metra
Brief summary
This is a Phase 1/2, first-in-human (FIH) safety, proof-of-concept, two-part study of the genetically-engineered EGEN-5784 liver in combination with the metra® extra-corporeal liver cross-circulation (ELC) system in participants with Grade 2 to Grade 3 acute-on-chronic liver failure (ACLF) and hepatic encephalopathy Grade 1-3. The metra® device has been modified for the purposes of cross-circulation with an extra-corporeal porcine liver. The EGEN-5784 liver and metra® ELC system are designed to support liver function during the treatment period
Detailed description
This is a Phase 1/2, first-in-human (FIH) safety, proof-of-concept, two-part study of the genetically engineered EGEN-5784 liver in combination with the metra® extra-corporeal liver cross-circulation (ELC) system in participants with Grade 2 to Grade 3 acute-on-chronic liver failure (ACLF) and hepatic encephalopathy Grade 1-3. The metra® device has been modified for the purposes of cross-circulation with an extra-corporeal porcine liver. The EGEN-5784 liver and metra® ELC system are designed to support liver function during the treatment period In Part 1, up to 6 participants will be enrolled and undergo ELC for up to 2 centers in the US. In Part 2, up to 14 participants will be enrolled and undergo ELC at approximately 8 centers in the US. The study will assess the safety of the ELC used to support liver function in patients with acute on chronic liver failure. Safety will be assessed based on Adverse Events Serious Adverse Events during the 28 days post-ELC and for the duration of the study. Unanticipated adverse device effects will be assessed during the ELC. Liver-related laboratory parameters will be assessed during the ELC treatment, and during the follow up period.
Interventions
DEVICEmetra® Extracorporeal Liver Cross-Circulation (ELC) system (OrganOx)
Perfusion circuit/device enabling extracorporeal cross-circulation between the participant and the EGEN-5784 porcine liver. Planned support up to 72 h in Part 1 and up to 120 h in Part 2 if no safety/stopping criteria are met, with ICU-level monitoring and protocol-defined operating parameters.
BIOLOGICALEGEN-5784 (genetically engineered porcine liver)
Viable porcine liver from a genetically engineered donor (EGEN-5784) used for temporary extracorporeal cross-circulation support. The liver is not implanted; it is perfused in a closed circuit with the participant under continuous monitoring and predefined stopping rules per protocol.
Sponsors
eGenesis, INC
OrganOx Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female, age 18 to 70 years, inclusive * Not eligible for transplantation at the time of enrollment * Diagnosis of Grade 2 to 3 ACLF according to the European Association for the Study of Chronic Liver Failure (EASL-CLIF) definition and Chronic Liver Failure Consortium-organ failure score (CLIF-C-OF) ≥10 * Hepatic encephalopathy Grade 1 to 3 by West Haven Criteria * Written consent provided by participant or LAR (if participant lacks capacity, e.g., due to hepatic encephalopathy) prior to conduct of any study procedures Key
Exclusion criteria
* Prior solid organ transplant * Fulminant hepatic failure without underlying liver disease * Non-biological artificial liver extracorporeal liver support (e.g., molecular adsorbent recirculating system) or bioartificial liver support systems within 30 days prior to EGEN-5784 liver perfusion * Liver dysfunction due to trauma, or extra-hepatic cholestasis * Any uncontrolled ongoing active infection * History or active human immunodeficiency virus (HIV) infection or acute hepatitis B virus (HBV) * Chronic HBV or active hepatitis C * Diagnosis of cancer requiring active ongoing treatment, e.g., chemotherapy, radiation therapy * Severe concomitant cardiovascular disease defined as congestive heart failure Class III and IV * Significant acute or chronic pulmonary disease requiring ventilator support or diagnosed with chronic obstructive pulmonary disease Global Obstructive Lung Disease \[GOLD\] stage III or IV disorder * Active uncontrolled bleeding (i.e., any major blood loss requiring ≥2 units of pRBCs within the last 48 hours prior to screening) * Any other health condition, including illicit drug use, that would preclude participation in the study in the judgement of the PI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TESAE's | From ELC initiation to 28 days post-ELC initiation | Incidence of Treatment-Emergent Serious Adverse Event |
| Incidence of AESIs | From ELC initiation through 28 days post ELC initation | Incidence of Adverse Event of Special Interest |
| Incidence of Device Deficiencies | From metra® initiation through metra® ELC termination (assessed continuously during the ELC procedure; up to 72 hours in Part 1 and 120 hours in Part 2) | — |
| Incidence of UADEs | From metra® initiation through metra® ELC termination (assessed continuously during the ELC procedure; up to 72 hours in Part 1 and 120 hours in Part 2) | Incidence of Unanticipated Adverse Device Effect |
Secondary
| Measure | Time frame |
|---|---|
| Change in blood ammonia (NH₃), measured in µmol/L | From Baseline to 28 days post ELC initiation |
| Change in total bilirubin and direct bilirubin measured in mg/dL | From Baseline to 28 days post ELC initiation |
| Change in coagulation parameters, measured by international normalized ratio (INR) | From Baseline to 28 days post ELC initiation |
| Change in ACLF score | From Baseline to 28 days post ELC initiation |
| Change in West Haven criteria for hepatic encephalopathy | Baseline to 28 days post ELC initiation |
Countries
United States
Contacts
CONTACTPatient Inquires
Outcome results
None listed