A Clinical Study on the Safety, Tolerability, and Preliminary Efficacy of Hepatocyte-like Cell Injection for the Prevention and Treatment of Small-for-Size Syndrome
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of adverse events related to hepatocyte-like cell injection
研究概览
简要总结
To evaluate the safety, tolerability, and preliminary efficacy of rectus sheath injection of hepatocyte-like cells in the treatment and prevention of small-for-size syndrome, with the ultimate goal of improving patient survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be diagnosed with liver failure or small-for-size syndrome based on clinical presentation.
- •（Acute Liver Failure (ALF) An acute onset of liver failure characterized by hepatic encephalopathy of grade II or higher within 4 weeks, in a patient without pre-existing liver disease.
- •Acute-on-Chronic Liver Failure (ACLF) A complex clinical syndrome characterized by acute deterioration of liver function, triggered by precipitating events, in patients with underlying chronic liver disease (with or without cirrhosis). It manifests as single or multiple organ failure(s) and is associated with high short-term mortality (28-day mortality rate ≥ 15%).
- •Chronic Liver Failure (CLF) A state of chronic hepatic decompensation occurring progressively in patients with cirrhosis. It is primarily characterized by recurrent ascites and/or hepatic encephalopathy resulting from progressively declining liver function.
- •Small-for-Size Syndrome (SFSS) Diagnosis is established according to the International Liver Transplantation Society (ILTS) 2023 guidelines on SFSS.） ② Patients must agree to undergo intramuscular injection of cells into the rectus sheath.
排除标准
- •Subjects meeting any of the following criteria will be excluded from the study:
- •Presence of severe, life-threatening extrahepatic systemic diseases.
- •Uncontrolled active infection or hemorrhage.
- •Pregnancy or lactation in female patients.
- •History of severe allergic reactions or known hypersensitivity to CiPS-derived cell products or blood products.
- •Inability to undergo phlebotomy due to peripheral vascular collapse.
- •Inability or unwillingness to provide informed consent or comply with the study procedures.
- •Unwillingness to receive CiPS-based therapy.
研究组 & 干预措施
Small-for-Size Syndrome
On the basis of standard medical therapy, patients will receive an intramuscular injection of CiPS-derived hepatocyte cells into the rectus sheath.
Cell quantity: The prespecified therapeutic dose is 1.2×10⁸/kg. To ensure safety, the first patient receives 50% of that dose (0.6×10⁸/kg). After safety confirmation, subsequent patients receive the standard 1.2×10⁸/kg (adjusted based on individual rectus sheath capacity, with actual dose recorded).
干预措施: Hepatocyte-like cell administration via rectus sheath intramuscular injection (Drug)
High risk of small-for-size syndrome
On the basis of standard medical therapy, patients will receive an intramuscular injection of CiPS-derived hepatocyte cells into the rectus sheath.
Cell quantity: The prespecified therapeutic dose is 1.2×10⁸/kg. To ensure safety, the first patient receives 50% of that dose (0.6×10⁸/kg). After safety confirmation, subsequent patients receive the standard 1.2×10⁸/kg (adjusted based on individual rectus sheath capacity, with actual dose recorded).
干预措施: Hepatocyte-like cell administration via rectus sheath intramuscular injection (Drug)
结局指标
主要结局
Incidence of adverse events related to hepatocyte-like cell injection
时间窗: within 7 days after injection
Defined as all adverse events clearly associated with the injection procedure occurring within 7 days after injection, including puncture-site hematoma, secondary infection, etc. The estimated incidence of injection-related adverse events is no more than 25%.
Plasma Ammonia
时间窗: Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment.
Ammonia levels in μmol/L will be measured from blood samples. The outcome will be reported as the change from baseline in plasma ammonia levels at each specified time point.
Serum Direct Bilirubin
时间窗: Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment.
Direct bilirubin levels in mg/dL (or μmol/L) will be measured from blood samples. The outcome will be reported as the change from baseline in direct bilirubin levels at each specified time point.
Serum Total Bilirubin
时间窗: Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment.
Total bilirubin levels in mg/dL (or μmol/L) will be measured from blood samples. The outcome will be reported as the change from baseline in total bilirubin levels at each specified time point.
Serum Aspartate Aminotransferase (AST)
时间窗: Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment.
AST levels in U/L will be measured from blood samples. The outcome will be reported as the change from baseline in AST levels at each specified time point.
Serum Alanine Aminotransferase (ALT)
时间窗: Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment.
ALT levels in U/L will be measured from blood samples. The outcome will be reported as the change from baseline in ALT levels at each specified time point.
Incidence of short-term adverse events related to the hepatocyte-like cell product
时间窗: within 1 month after injection
Defined as adverse events clearly associated with the hepatocyte-like cell product occurring within 1 month after injection, including fever, rash, hypotension, allergic reactions, etc. The estimated incidence of short-term adverse events related to the hepatocyte-like cell product is no more than 25%.
Incidence, severity, and prognosis of small-for-size syndrome
时间窗: Within 3 months after injection
The incidence, severity grade, and patient prognosis of small-for-size syndrome will be recorded, using patients who did not receive hepatocyte-like cell injection during the same period as historical controls.
Coagulation Function
时间窗: Blood samples will be collected before injection, at 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-injection.
(including Prothrombin Time \[PT\], Activated Partial Thromboplastin Time \[APTT\], International Normalized Ratio \[INR\], and Prothrombin Time Activity \[PTA\]). PT and APTT will be measured in seconds, INR will be reported as a ratio, and PTA will be measured as a percentage (%). The outcome will be reported as the change from baseline in each coagulation parameter at each specified time point.
Survival Rate
时间窗: 1 year following injection
Adverse Reaction Rate
时间窗: within 1 year following injection
Adverse reactions related to hepatocyte-like cell injection can be categorized into two types: i) injection-related adverse reactions (such as bleeding and infection), and ii) cell product-related adverse reactions (including but not limited to immune rejection and tumorigenicity).
次要结局
- Absence of Abnormal Fat Deposition on T1-weighted Fat-Suppressed (T1W-FS) MRI(MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.)
- Heart Rate(Measured at before treatment, and at 1, 3, 6, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 2 and 3 post-treatment.)
- Respiratory Rate(Measured at before treatment, and at 1, 3, 6, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 2 and 3 post-treatment.)
- Blood Pressure(Measured at before treatment, and at 1, 3, 6, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 2 and 3 post-treatment.)
- Graft Morphological Stability on T2-weighted Fat-Suppressed (T2W-FS) MRI(MRI assessments will be performed at baseline (pre-treatment), and at Day 7, 14, Month 1, 2, and 3 post-treatment.)
- Graft Signal Characteristics on T2-weighted Fat-Suppressed (T2W-FS) MRI(MRI assessments will be performed at baseline (pre-treatment), and at Day 7, 14, Month 1, 2, and 3 post-treatment.)
- Rectus Sheath Ultrasound Examination(Before injection, 12 hours post-injection, day 3, day 7 , day 14, and months 1, 2, and 3.)
- Change from baseline in serum levels of tumor markers measured in ng/mL(Blood samples will be collected before injection, and on days 14, as well as at months 1, 2, and 3 post-injection.)
- Change from baseline in serum levels of tumor markers measured in μg/L(Blood samples collected before injection, and on day 14, as well as at months 1, 2, and 3 post-injection.)
- Incidence of medium-to-long-term adverse events related to the hepatocyte-like cell product(1to 3 month after injection)
- Serum Aspartate Aminotransferase (AST)(Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Consciousness Level as assessed by Glasgow Coma Scale (GCS)(Assessed at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Graft Morphological Stability on T2-weighted Fat-Suppressed (T2W-FS) MRI(MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.)
- Graft Signal Characteristics on T2-weighted Fat-Suppressed (T2W-FS) MRI(MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.)
- Serum Alanine Aminotransferase (ALT)(Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Heart Rate(Measured at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Blood Pressure)(Measured at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Serum Total Bilirubin(Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Serum Direct Bilirubin(Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Plasma Ammonia(Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Respiratory Rate(Measured at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.)
- Absence of Abnormal Fat Deposition on T1-weighted Fat-Suppressed (T1W-FS) MRI(MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.)
研究者
Zhi-Jun Zhu
Principal Investigator
Beijing Friendship Hospital