Safety, Tolerability, and Preliminary Efficacy of Hepatocyte-like Cell Injection for the Prevention and Treatment of Small-for-Size Syndrome

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Hepatocyte-like cell administration via rectus sheath intramuscular injection
  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).

Первичные конечные точки

• Incidence of adverse events related to hepatocyte-like cell injection [Срок оценки: within 7 days after injection]
• Plasma Ammonia [Срок оценки: 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.]
• Serum Direct Bilirubin [Срок оценки: 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.]
• Serum Total Bilirubin [Срок оценки: 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.]
• Serum Aspartate Aminotransferase (AST) [Срок оценки: 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.]
• Serum Alanine Aminotransferase (ALT) [Срок оценки: 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.]
• Incidence of short-term adverse events related to the hepatocyte-like cell product [Срок оценки: within 1 month after injection]
• Incidence, severity, and prognosis of small-for-size syndrome [Срок оценки: Within 3 months after injection]
• Coagulation Function [Срок оценки: 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.]

Вторичные конечные точки (10)

• Heart Rate [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: MRI assessments will be performed at baseline (pre-treatment), and at Day 7, 14, Month 1, 2, and 3 post-treatment.]
• Absence of Abnormal Fat Deposition on T1-weighted Fat-Suppressed (T1W-FS) MRI [Срок оценки: MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.]
• Rectus Sheath Ultrasound Examination [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 1to 3 month after injection]

Критерии участия

Критерии включения

• 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.

Критерии исключения

\-

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.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Friendship Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT07276568 · BFH20251030001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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