EGEN-5784 Porcine Liver With the Metra® ELC Device

Официальное название

A Phase 1, First-in-Human Safety and Proof-of-Concept Study to Evaluate EGEN-5784 Porcine Liver (Drug Product) in Combination With the Metra® Extra-Corporeal Liver Cross-Circulation Device in Participants With Acute-on-Chronic Liver Failure

Обзор

This is a Phase 1, 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 device are designed to support liver function during the treatment period

Подробное описание

This is a Phase 1, 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 device 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.

Вмешательства

• Устройство metra® 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.
• Биопрепарат EGEN-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.

Первичные конечные точки

• Incidence of TESAE's [Срок оценки: From ELC initiation to 28 days post-ELC initiation]
• Incidence of AESIs [Срок оценки: From ELC initiation through 28 days post ELC initation]
• Incidence of Device Deficiencies [Срок оценки: 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 [Срок оценки: 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)]

Вторичные конечные точки (5)

• Change in blood ammonia (NH₃), measured in µmol/L [Срок оценки: From Baseline to 28 days post ELC initiation]
• Change in total bilirubin and direct bilirubin measured in mg/dL [Срок оценки: From Baseline to 28 days post ELC initiation]
• Change in coagulation parameters, measured by international normalized ratio (INR) [Срок оценки: From Baseline to 28 days post ELC initiation]
• Change in ACLF score [Срок оценки: From Baseline to 28 days post ELC initiation]
• Change in West Haven criteria for hepatic encephalopathy [Срок оценки: Baseline to 28 days post ELC initiation]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Washington University — St Louis
• University of Wisconsin — Madison

Идентификаторы

NCT: NCT07429838 · EGEN-5784-CL-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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