A Phase 1/2, 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 System in Participants With Acute-on-Chronic Liver Failure
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Incidence of TESAE's
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
EGEN-5784 + metra® Extracorporeal Liver Cross-Circulation (ELC)
Participants with Grade 2-3 ACLF receive extracorporeal cross-circulation using a genetically engineered porcine liver (EGEN-5784) connected via the metra® ELC system, in addition to institutional standard of care. No comparator arm is included
干预措施: EGEN-5784 (genetically engineered porcine liver) (Biological)
EGEN-5784 + metra® Extracorporeal Liver Cross-Circulation (ELC)
Participants with Grade 2-3 ACLF receive extracorporeal cross-circulation using a genetically engineered porcine liver (EGEN-5784) connected via the metra® ELC system, in addition to institutional standard of care. No comparator arm is included
干预措施: metra® Extracorporeal Liver Cross-Circulation (ELC) system (OrganOx) (Device)
结局指标
主要结局
Incidence of TESAE's
时间窗: From ELC initiation to 28 days post-ELC initiation
Incidence of Treatment-Emergent Serious Adverse Event
Incidence of AESIs
时间窗: From ELC initiation through 28 days post ELC initation
Incidence of Adverse Event of Special Interest
Incidence of Device Deficiencies
时间窗: 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
时间窗: 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
次要结局
- 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)