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

Alcoholic Cirrhosis Clinical Trial

— Cellgram-LC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04689152
• Other study ID #: PMC-P-07
• Status: Recruiting
• Phase: Phase 3
• Start date: March 2, 2021
• Est. completion date: January 2, 2028

Study information

• Verified date: March 2024
• Source: Pharmicell Co., Ltd.
• Contact: JIYEOUN JEONG
• Phone: 82-2-3496-0134
• Email: jyjeong[@]pharmicell.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 2, 2028
• Est. primary completion date: August 2, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 71 Years

Eligibility

Inclusion Criteria:

1. At the time of screening, 19 or 70 years

2. 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)

3. Those whose survival period is more than 1 year when judged by the tester

4. Those who can perform hepatic artery catheterization by inserting a catheter into the hepatic artery at the judgment of the examiner

5. 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

6. Those who can conduct clinical trials according to the clinical trial protocol

7. A person who has consented in writing to voluntarily participate in this clinical trial

Exclusion Criteria:

1. 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

2. Patients who underwent portal systemic shunting in the jugular vein

3. Patients with alcohol consumption or hepatotoxic drugs within 6 months prior to screening

4. Persons taking high-dose steroids, immunosuppressants, or antimicrobials due to severe infections for at least 1 month of screening

5. Those who have major surgical operations, long-term biopsy, or significant trauma as judged by the investigator within 3 months before screening

6. Those whose history of gastrointestinal bleeding is confirmed within 10 days of screening

7. 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)

8. serologic test result (HIV, HAV, HBV, HCV, Syphilis infection) positive factor

9. Patients unable to collect bone marrow due to bone marrow disease

10. Those with a history of gentamicin hypersensitivity reaction

11. Pregnant or lactating women

12. Those with substance abuse experience within 1 year before screening

13. Those who participated in other clinical trials within one month before screening and administered (or applied) clinical trial drugs (or medical devices)

14. Those who previously participated in clinical trials related to cell therapy

15. Patients judged to be inappropriate to participate in this clinical trial due to complications, etc., when judged by the investigator before screening or registration

Related Conditions & MeSH terms

• Alcoholic Cirrhosis
• Fibrosis
• Liver Cirrhosis
• Liver Cirrhosis, Alcoholic

Intervention

Biological:
• Cellgram-LC
Patients will receive single injection of Cellgram-LC(mesenchymal stem cell) hepatic artery.

Locations

Country	Name	City	State
Korea, Republic of	Soonchunhyang University Hospital	Bucheon
Korea, Republic of	Soonchunhyang University Hospital	Cheonan
Korea, Republic of	Gangwon National University Hospital	ChunCheon
Korea, Republic of	Hallym Univ. Medical Center	ChunCheon
Korea, Republic of	Gangneung Asan Hospital	Gangneung-si
Korea, Republic of	Eunpyeong St. Mary's Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Soonchunhyang University Hospital	Seoul
Korea, Republic of	Wonju Severance Christian Hospital	Wonju
Korea, Republic of	Yongin Severance Hospital	Yongin

Sponsors (1)

Lead Sponsor	Collaborator
Pharmicell Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	a-fetoprotein test	Two sample t-test or Wilcoxon rank-sum test is performed to test the difference between the two groups for the results of tumor marker test (AFP) at each time point.	week -6, month 3, 6, 9, 12, 18, 24
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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