Clinical Trial to Evaluate the Efficacy and Safety of Cellgram-LC Administration in Patients With Alcoholic Cirrhosis (Cellgram-LC)
Primary Purpose
Alcoholic Cirrhosis
Status
Recruiting
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Cellgram-LC
Sponsored by
About this trial
This is an interventional treatment trial for Alcoholic Cirrhosis
Eligibility Criteria
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
Sites / Locations
- Soonchunhyang University HospitalRecruiting
- Soonchunhyang University HospitalRecruiting
- Gangwon National University HospitalRecruiting
- Hallym Univ. Medical CenterRecruiting
- Gangneung Asan HospitalRecruiting
- Eunpyeong St. Mary's HospitalRecruiting
- Korea University Anam HospitalRecruiting
- Seoul National University HospitalRecruiting
- Soonchunhyang University HospitalRecruiting
- Wonju Severance Christian HospitalRecruiting
- Yongin Severance HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control group
Injection group: Cellgram-LC
Arm Description
Best Supportive care
Within 1 month after extracting bone marrow, directly inject 7X10^7 autologous bone marrow-derived mesenchymal stem cells within liver through the hepatic artery.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT04689152
First Posted
December 21, 2020
Last Updated
August 17, 2021
Sponsor
Pharmicell Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04689152
Brief Title
Clinical Trial to Evaluate the Efficacy and Safety of Cellgram-LC Administration in Patients With Alcoholic Cirrhosis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2021 (Actual)
Primary Completion Date
March 2, 2026 (Anticipated)
Study Completion Date
March 2, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmicell Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase III clinical trial is designed to evaluate the efficacy and safety of autologous Mesenchymal Stem Cells (MSC) injected hepatic artery.
Detailed Description
To evaluate the efficacy and efficacy for 60 months after a single dose of Cellgram-LC in patients with alcoholic liver cirrhosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Best Supportive care
Arm Title
Injection group: Cellgram-LC
Arm Type
Experimental
Arm Description
Within 1 month after extracting bone marrow, directly inject 7X10^7 autologous bone marrow-derived mesenchymal stem cells within liver through the hepatic artery.
Intervention Type
Biological
Intervention Name(s)
Cellgram-LC
Other Intervention Name(s)
Autologous bone marrow-derived mesenchymal stem cell
Intervention Description
Patients will receive single injection of Cellgram-LC(mesenchymal stem cell) hepatic artery.
Primary Outcome Measure Information:
Title
Transplant free survival (TFS)
Description
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.
Time Frame
For 3 years
Secondary Outcome Measure Information:
Title
Survival rate
Description
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.
Time Frame
month 24 and 36
Title
Change amount of Child-Pugh score
Description
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.
Time Frame
week -6 and 0
Title
Change amount of MELD score
Description
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.
Time Frame
week -6 and 0
Title
Change amount of Liver function test
Description
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.
Time Frame
month 0, 1, 3, 6, 9, 12, 18 and 24
Title
Change amount of Fibrosis-4
Description
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.
Time Frame
month 0, 6, 12, 18 and 24
Title
Change amount of FibroScanⓇ
Description
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.
Time Frame
week -6 and 0
Title
Change amount of EQ-5D
Description
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.
Time Frame
month -1, 6, 12, 18 and 24
Title
Change amount of EQ-VAS
Description
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.
Time Frame
month -1, 6, 12, 18 and 24
Other Pre-specified Outcome Measures:
Title
α-fetoprotein test
Description
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.
Time Frame
week -6, month 3, 6, 9, 12, 18, 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
71 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
JIYEOUN JEONG
Phone
82-2-3496-0134
Email
jyjeong@pharmicell.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Moonyoung Kim
Organizational Affiliation
Wonju Severance Christian Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Soonchunhyang University Hospital
City
Bucheon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sang-gyun Kim
Email
mcnulty@schmc.ac.kr
Facility Name
Soonchunhyang University Hospital
City
Cheonan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
hongsoo kim
Email
khskhs@sch.ac.kr
Facility Name
Gangwon National University Hospital
City
ChunCheon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daehee Choi
Email
dhchoi-md@kangwon.ac.kr
Facility Name
Hallym Univ. Medical Center
City
ChunCheon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ki-tae Seok
Email
diarrhea100@hanmail.net
Facility Name
Gangneung Asan Hospital
City
Gangneung-si
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gapjin Cheon
Email
1000@gnah.co.kr
Facility Name
Eunpyeong St. Mary's Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sihyeon Bae
Email
baesh@catholic.ac.kr
Facility Name
Korea University Anam Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yeonseok Seo
Email
drseo@korea.ac.kr
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeonghwan Yoon
Email
yoonjh@snu.ac.kr
Facility Name
Soonchunhyang University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jaeyoung Jang
Email
jyjang@schmc.ac.kr
Facility Name
Wonju Severance Christian Hospital
City
Wonju
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moonyoung Kim
Email
drkimmy@yonsei.ac.kr
First Name & Middle Initial & Last Name & Degree
Sun-gu Baek
Facility Name
Yongin Severance Hospital
City
Yongin
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jakyung Kim
Email
ceciliak@yuhs.ac
12. IPD Sharing Statement
Learn more about this trial
Clinical Trial to Evaluate the Efficacy and Safety of Cellgram-LC Administration in Patients With Alcoholic Cirrhosis
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