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

Early Phase 1Enrolling By InvitationNCT07276568

Zhi-Jun Zhu12 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Small-for-size Syndrome

Interventions

Hepatocyte-like cell administration via rectus sheath intramuscular injectionDRUG

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).

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: \- Subjects meeting any of the following criteria will be excluded from the study: 1. Presence of severe, life-threatening extrahepatic systemic diseases. 2. Uncontrolled active infection or hemorrhage. 3. Pregnancy or lactation in female patients. 4. History of severe allergic reactions or known hypersensitivity to CiPS-derived cell products or blood products. 5. Inability to undergo phlebotomy due to peripheral vascular collapse. 6. Inability or unwillingness to provide informed consent or comply with the study procedures. 7. Unwillingness to receive CiPS-based therapy.

Locations (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, Province, China

Outcomes

Primary Outcomes

Incidence of adverse events related to hepatocyte-like cell 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%.

Time frame: within 7 days after injection

Plasma Ammonia

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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)

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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

Heart Rate

Heart rate will be measured in beats per minute (bpm) in a supine or sitting position after the participant has rested for at least 5 minutes. The outcome will be reported as the change from baseline in heart rate at each specified time point.

Time frame: 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

Respiratory rate will be measured in breaths per minute (brpm). The outcome will be reported as the change from baseline in respiratory rate at each specified time point.

Time frame: 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

Blood pressure will be measured in millimeters of mercury (mmHg) in a supine or sitting position after the participant has rested for at least 5 minutes.

Time frame: 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

The graft site within the left rectus abdominis muscle will be assessed by T2W-FS MRI for morphological stability. The outcome is based on the presence or absence of significant changes in location, shape, and size compared to the baseline (post-engraftment) scan. The absence of mass effect, displacement, or deformation of the surrounding muscle will be documented. Stability in these parameters over time will be considered a favorable outcome, while significant deviation will be reported as an adverse event.

Time frame: 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

The graft site will be assessed by T2W-FS MRI for signal intensity characteristics. The outcome is based on the signal intensity and pattern (e.g., homogeneous, stippled, nodular) relative to the surrounding normal muscle tissue. A stable or resolving signal pattern without the development of focal, nodular, or mass-like high signal intensity will be considered a favorable outcome. The development of new or evolving high-signal areas suggestive of abnormal growth will be reported.

Time frame: 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

The graft site will be assessed by T1W-FS MRI for the absence of abnormal fat deposition, a key indicator for teratoma formation. The outcome is a binary assessment (Yes/No) of whether the signal intensity of the graft region is isointense to surrounding normal muscle tissue.

Time frame: MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.

Rectus Sheath Ultrasound Examination

With the subject in a supine position and the abdomen fully exposed, an ultrasound probe is placed along the orientation of the rectus abdominis muscle, performing longitudinal and transverse scans. The thickness of the rectus sheath (vertical distance from the inner edge of the anterior sheath to the anterior edge of the posterior sheath) is measured. After injection of hepatocyte-like cells, the same measurements are repeated at each follow-up time point. Meanwhile, special attention is paid to the presence of any abnormal echoic areas within the rectus sheath (e.g., hematoma, effusion, abnormal cell aggregation, or space-occupying lesions), and their location, size, margins, and internal echo characteristics are recorded. Color Doppler mode is used to assess whether abnormal blood flow signals are present in the injection area.

Time frame: 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

Including Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA), Cancer Antigen 125 (CA125), Carbohydrate Antigen 19-9 (CA19-9), Total Prostate-Specific Antigen (tPSA), Free Prostate-Specific Antigen (fPSA), Complexed Prostate-Specific Antigen (c-PSA), Carbohydrate Antigen CA242, Carbohydrate Antigen CA724, Carbohydrate Antigen CA50, and Cancer Antigen 15-3 (CA153). For markers specific to males (tPSA, fPSA, c-PSA) or females (CA153), only applicable subjects will be tested. Unit of Measure: ng/mL

Time frame: 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

Including Neuron-Specific Enolase (NSE), Cytokeratin 19 Fragment (CYFRA21-1), Squamous Cell Carcinoma Antigen (SCC), and Human Epididymis Protein 4 (HE4). For HE4 (female-specific), only applicable subjects will be tested. Unit of Measure: μg/L

Time frame: 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

Defined as adverse events clearly associated with the hepatocyte-like cell product occurring between 1 month and 3 months after injection, including non-targeted cell migration, abnormal proliferation, etc. The estimated incidence of medium-to-long-term adverse events related to the hepatocyte-like cell product is no more than 15%.

Time frame: 1to 3 month after injection