A Phase 2a, Open Label, Dose Escalation Study for Safety, Tolerability, and Efficacy of Hepatocyte Transplantation Into Periduodenal Lymph Nodes Among Subjects With End-Stage Liver Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Dosage Selection
研究概览
简要总结
This Phase 2a clinical trial is a dose escalation study of the safety, tolerability, and efficacy of hepatocyte transplantation into lymph nodes via endoscopic ultrasound among subjects with end-stage liver disease.
详细描述
This safety, tolerability, and efficacy study includes an open-label dose-escalation phase for up to 12 subjects with end-stage liver disease (ESLD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is no masking in the open-label dose escalation phase.
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
- •Have read, understood, and signed the informed consent form (ICF).
- •Adults of either gender and ages 18 to 70 years old with a diagnosis of ESLD due to alcohol, chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections, autoimmune hepatitis, primary sclerosis cholangitis, primary biliary cirrhosis (cholangitis), cirrhosis as the result of Wilson disease, hemochromatosis, sarcoidosis and alpha 1 antitrypsin deficiency, cryptogenic cirrhosis, and nonalcoholic steatohepatitis cirrhosis with a MELD-Na score >10 and <25 at screening.
- •Subjects must have a body mass index (BMI) <
- •Subjects with HCV associated ESLD must have been treated and demonstrate 24 weeks of negative HCV ribonucleic acid (RNA).
- •Subjects with HBV must be on stable therapy for 6 months and have HBV deoxyribonucleic acid <500 c/mL.
- •Women of childbearing potential (WOCBP) or sexual partners of male subjects who are WOCBP must be able and willing to use at least 1 highly effective method of contraception during the study and for 1 month after the last study visit. A female subject is considered to be a WOCBP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy; HMA, 2014). For the definition and list of highly effective methods of contraception, see Appendix
- •Has stable control of portal hypertension and upper gastrointestinal bleeding with medical therapy and/or endoscopic therapy.
- •If the subject has undergone a TIPS procedure for the clinical management of portal hypertension, they must be stable after the successful TIPS procedure, and not experiencing serious complications from the TIPS procedure itself (e.g., infection and intractable hepatic encephalopathy).
- •Has blood urea nitrogen (BUN) <80 mg/dL.
- •Has an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m
- •Agrees to avoid alcohol consumption during the study.
- •Is willing and able to comply with all requirements of the study protocol.
排除标准
- •Has primary hepatic neoplasms (hepatocellular carcinoma and cholangiocarcinoma).
- •Has active and/or uncontrolled severe infections requiring hospitalization and prolonged antimicrobial therapy.
- •Has severe coagulopathy (international normalized ratio [INR] >2, and/or platelet count <50,000/μL).
- •Has psychiatric and/or social issues that could lead to noncompliance.
- •Has an extrahepatic neoplastic disease requiring active chemotherapy, immunotherapy, and/or surgical resection.
- •Has previously treated neoplastic disease with less than a 2-year cancer free period.
- •Pregnant and lactating women should not be in the study.
- •Known hypersensitivity to human serum albumin.
- •Subjects with uncontrolled hypertension (defined as a diastolic blood pressure of 110 mmHg or higher).
- •Has recurrent/intractable ascites refractory to diuretics and requiring periodic large volume paracentesis.
- •Has primary alcoholic liver disease and has not demonstrated abstinence for at least 24 weeks (6 months) prior to enrollment while attending mandatory rehab programs (e.g., Alcoholics Anonymous) and psychotherapy.
- •Has grade 3 esophageal varices requiring the continuous use of propranolol and cannot afford to have this medication withheld and/or discontinued.
- •Has a Child-Turcotte-Pugh (CTP) Class of C.
- •Is receiving or plans to receive treatment with another investigational product or device.
研究组 & 干预措施
LYG-LIV0001
Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.
干预措施: LYG-LIV0001 (Biological)
结局指标
主要结局
Dosage Selection
时间窗: Week 12
The primary objective of the dose escalation is to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment
Efficacy of Engraftment of Hepatocytes in to Lymph Nodes
时间窗: Week 12
The primary efficacy objective of the dose escalation is to determine whether AH engraftments into the periduodenal lymph nodes in subjects with end-stage liver disease is efficacious in addressing some of the signs and symptoms of end-stage liver disease
Safety of Engraftment of Hepatocytes in to Lymph Nodes
时间窗: Week 12
The primary safety objective of the dose escalation is to determine whether AH engraftments into the periduodenal lymph nodes in subjects with end-stage liver disease is safe as determined by the number/severity of adverse events
次要结局
- Effectiveness of Selected Treatment to Modify the Liver Function Panel(Week 52)