Clinical Trial to Evaluate the Efficacy and Safety of Cellgram-LC Administration in Patients With Alcoholic Cirrhosis

Study Overview
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Brief Summary
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This phase III clinical trial is designed to evaluate the efficacy and safety of autologous Mesenchymal Stem Cells (MSC) injected hepatic artery.

Detailed Description
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To evaluate the efficacy and efficacy for 60 months after a single dose of Cellgram-LC in patients with alcoholic liver cirrhosis.

Official Title
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A Multicenter, Randomized, Open-label Phase III Clinical Trial to Evaluate Efficacy and Safety of the Cellgram-LC in Patients With Alcoholic Liver Cirrhosis

Conditions
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Alcoholic Cirrhosis

Intervention / Treatment
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* Biological: Cellgram-LC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At the time of screening, 19 or 70 years Patients diagnosed with alcoholic cirrhosis by combining alcohol history, imaging and pathological examination results, and clinical symptoms at screening, and belonging to Child-Pugh grade B or C (Child-Pugh score of 7 or more) Those whose survival period is more than 1 year when judged by the tester Those who can perform hepatic artery catheterization by inserting a catheter into the hepatic artery at the judgment of the examiner In the case of women of childbearing potential, a person who was confirmed negative in the pregnancy test at screening and agreed to use contraception* by the method permitted for this clinical trial during the clinical trial Those who can conduct clinical trials according to the clinical trial protocol A person who has consented in writing to voluntarily participate in this clinical trial Exclusion Criteria: Those with a history of solid cancer including Hepatocellular Carcinoma (HCC) (within 5 years before screening), those who have been diagnosed with solid cancer and are currently undergoing chemotherapy or those whose hepatocellular carcinoma has been confirmed by screening tests Patients who underwent portal systemic shunting in the jugular vein Patients with alcohol consumption or hepatotoxic drugs within 6 months prior to screening Persons taking high-dose steroids, immunosuppressants, or antimicrobials due to severe infections for at least 1 month of screening Those who have major surgical operations, long-term biopsy, or significant trauma as judged by the investigator within 3 months before screening Those whose history of gastrointestinal bleeding is confirmed within 10 days of screening Those whose medical history or accompanying diseases following the screening time is confirmed If you have not been diagnosed with a malignant blood disease (acute myelogenous leukemia, acute lymphocytic leukemia, non-Hodgkins lymphoma, Hodgkins lymphoma, multiple myelopathy) Severe aplastic anemia Liver transplant history Liver diseases of other causes besides alcoholic cirrhosis: hepatitis B and C, autoimmune liver disease (primary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis, etc.), weak liver toxicity, non-alcoholic fatty liver disease , NAFLD), Wilson's disease, iron excess, alpha-1-antitrypsin deficiency, etc.) Extrahepatic biliary stenosis Active portal vein or hepatic vein thrombosis Heart failure or respiratory failure Severe renal impairment (when the result of serum creatinine test exceeds 1.5 times the upper limit of normal) Acute or chronic infection requiring systemic treatment Severe coagulation disorder (if the tester judges it as a severe coagulation disorder or one of the following 1 to 3; 1. bleeding predisposition, 2. coagulation, 3. platelet≤50,000/mm3 and INR≥1.5) serologic test result (HIV, HAV, HBV, HCV, Syphilis infection) positive factor Patients unable to collect bone marrow due to bone marrow disease Those with a history of gentamicin hypersensitivity reaction Pregnant or lactating women Those with substance abuse experience within 1 year before screening Those who participated in other clinical trials within one month before screening and administered (or applied) clinical trial drugs (or medical devices) Those who previously participated in clinical trials related to cell therapy Patients judged to be inappropriate to participate in this clinical trial due to complications, etc., when judged by the investigator before screening or registration

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 71 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Best Supportive care | |
| Experimental: Injection group: Cellgram-LC<br>Within 1 month after extracting bone marrow, directly inject 7X10^7 autologous bone marrow-derived mesenchymal stem cells within liver through the hepatic artery. | Biological: Cellgram-LC<br>* Patients will receive single injection of Cellgram-LC(mesenchymal stem cell) hepatic artery.<br>* Other names: Autologous bone marrow-derived mesenchymal stem cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant free survival (TFS) | Transplant free survival (TFS), the median survival time and 95% confidence interval for each group were presented using the Kaplan-Meier method, and the difference in the survival distribution between the two groups was used as a Cox proportional hazards model corrected for stratification Black. | For 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate | For the survival rate, the survival rate and 95% confidence interval at each time point are presented using the Kaplan-Meier method, and the difference in survival rate between the two groups is tested using the Z statistic. | month 24 and 36 | 
| Change amount of Child-Pugh score | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. CP score was calculated using five factors: hepatic encephalopathy, prothrombin time, bilirubin, serum albumin, and ascites, and the score range was 5-15 points. In the Child-Pugh grade, scores of the five factors are summed and evaluated as A if it is less than 7 points, B if it is 7-9, and C if it exceeds 9 points. | week -6 and 0 | 
| Change amount of MELD score | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. The higher the score, the higher the mortality rate. | week -6 and 0 | 
| Change amount of Liver function test | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. | month 0, 1, 3, 6, 9, 12, 18 and 24 | 
| Change amount of Fibrosis-4 | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. | month 0, 6, 12, 18 and 24 | 
| Change amount of FibroScanⓇ | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. | week -6 and 0 | 
| Change amount of EQ-5D | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. The higher the score, the higher the quality of life. | month -1, 6, 12, 18 and 24 | 
| Change amount of EQ-VAS | In order to compare the difference between groups in the amount of change in each evaluation variable at the time of visit after cell administration/best supportive therapy compared to the baseline value, covariance analysis (ANCOVA) is performed by setting the baseline time point and stratification factor as a correction variable for each evaluation variable. The higher the score, the higher the quality of life. | month -1, 6, 12, 18 and 24 |