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Trial record 1 of 1 for:    NCT05948982
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Safety of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in Patients With Decompensated Hepatitis B Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05948982
Recruitment Status : Not yet recruiting
First Posted : July 17, 2023
Last Update Posted : July 17, 2023
Sponsor:
Information provided by (Responsible Party):
Asia Cell Therapeutics (Shanghai) Co., Ltd.

Brief Summary:

The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses of human umbilical cord mesenchymal stem cell injection in patients with decompensated hepatitis B cirrhosis, and to further explore the efficacy, pharmacodynamic profile and appropriate dose of administration to provide a basis for the use of safer and more effective treatments for patients with decompensated hepatitis B cirrhosis in the future.

Participants are required to sign an informed consent form and, after undergoing a series of tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group for intravenous infusion of human umbilical cord mesenchymal stem cells.


Condition or disease Intervention/treatment Phase
Decompensated Liver Cirrhosis Biological: Human Umbilical Cord Mesenchymal Stem Cells Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Trial to Evaluate the Safety, Tolerance and Efficacy of aCell Inj. of Allogeneic UC-MSCs in Patients With Decompensated Hepatitis B Cirrhosis
Estimated Study Start Date : July 30, 2023
Estimated Primary Completion Date : December 31, 2026
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Human Umbilical Cord Mesenchymal Stem Cells
The trial was divided into three dose groups: Low-dose group: 1000000 cells/kg Medium-dose group: 2000000 cells/kg High-does group: 4000000 cells/kg
Biological: Human Umbilical Cord Mesenchymal Stem Cells
The stem cell infusion route is peripheral intravenous infusion, once every 4 weeks for a total of 3 infusions. All subjects received experimental drugs and conventional treatment during the study period.




Primary Outcome Measures :
  1. Adverse Event (AE) [ Time Frame: Through study completion, an average of 1 year ]
    Adverse events that occurred during the trials

  2. Serious Adverse Event (SAE) [ Time Frame: Through study completion, an average of 1 year ]
    Serious adverse events that occurred during the trial

  3. Recommended dose for phase 2 clinical trial (RP2D) [ Time Frame: Through study completion, an average of 1 year ]
    Recommended dose for phase 2 clinical trial

  4. Dose-limiting toxicity (DLT) [ Time Frame: Through study completion, an average of 1 year ]
    Dose-limiting toxicity

  5. Maximum Tolerated Dose (MTD) [ Time Frame: Through study completion, an average of 1 year ]
    Maximum Tolerated Dose


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Through study completion, an average of 1 year ]
    Time of survival

  2. Rate of survival [ Time Frame: Through study completion, an average of 1 year ]
    Rate of survival without liver transplantation

  3. Child-Pugh [ Time Frame: Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The Child-Pugh score included a score for five indicators: hepatic encephalopathy, ascites, total bilirubin concentration, albumin concentration, and prothrombin time extension. For each indicator, the lowest score is 1, the highest score is 3, and the total score of each indicator is calculated. A higher score indicates more severe disease.

  4. MELD [ Time Frame: Day -14 - Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]

    The Model for End-stage Liver Disease is a scoring system based on serum creatinine, international standardized ratio, total bilirubin combined with the cause of cirrhosis to evaluate the liver function reserve and prognosis of patients with chronic liver disease. Calculating formula for R = 3.78 * ln [T - Bil (umol/L) / 17.1] ln (INR) + 9.57 + 11.2 * * ln Cr (umol/L) / 88.4 + 6.43 * the etiology.

    (Etiology: 0 for cholestatic cirrhosis and alcoholic cirrhosis, 1 for viral and other causes)


  5. Hepatic stiffness [ Time Frame: Day -14 - Day -1, Week 12, Week 20, Week 32, Week 56 ]
    Based on transient elastography fibroscan, observe the liver stiffness.

  6. Alanine aminotransferase (ALT) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of ALT

  7. Aspartate aminotransferase (AST) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of AST

  8. Total bilirubin (TBIL) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of TBIL

  9. γ-glutamyl transpeptidase (γ-GT) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of γ-GT

  10. Alkaline phosphatase (ALP) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of ALP

  11. Albumin (ALB) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of ALB

  12. Cholinesterase (CHE) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week12, Week 20, Week 32, Week 56 ]
    The concentration of CHE

  13. International Normalized Ratio (INR) [ Time Frame: Day -14 - Day -1, Day -1, Day 1, Day 28, Day 29, Day 56, Day 57, Week 12, Week 20, Week 32, W56 ]
    INR was calculated by the PT ratio of the reference plasma measured by thrombin to normal plasma and the ISI value marked by the reagent used. The higher the INR, the longer it takes for blood to clot

  14. Cluster of differentiation 3 (CD3) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CD3

  15. Cluster of differentiation 4 (CD4) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CD4

  16. Cluster of differentiation 8 (CD8) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CD8

  17. Regulatory T cells (Treg) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of Treg

  18. Helper T cell 17 (Th17) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of Th17

  19. Immunoglobulin A (IgA) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IgA

  20. Immunoglobulin G (IgG) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IgG

  21. Immunoglobulin M (IgM) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IgM

  22. Immunoglobulin E (IgE) [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IgE

  23. Alpha-Fetoprotein (AFP) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of AFP

  24. Alpha-Fetoprotein-L3 (AFP-13) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of AFP-L3

  25. Carcinoembryonic antigen (CEA) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CEA

  26. Carbohydrate antigen (CA19-9) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CA19-9

  27. Carbohydrate antigen 15-3 (CA15-3 ) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CA15-3

  28. Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA II) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of PIVKA II

  29. Incidence of liver cancer [ Time Frame: Through study completion, an average of 1 year ]
    Calculate the number of subjects who developed liver cancer during the trial after drug administration as a percentage of all subjects

  30. HBV-DNA [ Time Frame: Day -14-Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of HBV-DNA

  31. Eastern Cooperative Oncology Group (ECOG) [ Time Frame: Day -14-Day -1, Week 12, Week 20, Week 32, Week 56 ]
    The ECOG score is an indicator of a patient's general health and ability to tolerate treatment from their physical strength. The ECOG physical condition scoring standard scores 0-5 points. The higher the score is, the worse the physical condition of patient is.

  32. Incidence of complications associated with decompensated cirrhosis [ Time Frame: Through study completion, an average of 1 year ]
    Diagnosis and severity assessment of complications

  33. Incidence of hepatic failure [ Time Frame: Through study completion, an average of 1 year ]
    Proportion of subjects who developed liver failure

  34. SF-36 Quality of Life Score [ Time Frame: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The 36-item Short-Form Health Questionnaire (SF-36) is a universal measurement scale developed by the Medical Outcomes Study (MOS) in the United States. It consists of 36 entries covering eight areas: physical function, physical role, physical pain, general health, vitality, social function, emotional role, and mental health. Each section is scored from 0 to 100 points. The score directly reflects the quality of health, the higher the score, the better the function of this aspect, the higher the quality of life.

  35. Chronic Liver Disease Questionnaire [ Time Frame: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    The Chronic Liver Disease questionnaire was designed to measure the overall body feeling of the participants within the last two weeks. The total score of the questionnaire ranges from 29 points to 203 points, and the lower the score, the worse the physical condition

  36. EQ-5D-5L [ Time Frame: Day -14-Day -1, Day -1, Day 28, Day 56, Week 12, Week 20, Week 32, Week 56 ]
    Health questionnaire about subjects' condition.


Other Outcome Measures:
  1. IL-1β (Interleukin-1β) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IL-1β

  2. IL-6 (Interleukin-6) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IL-6

  3. IL-8 (Interleukin-8) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IL-8

  4. IL-8 (Interleukin-10) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IL-10

  5. IL-8 (Interleukin-12) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IL-12

  6. IL-8 (Interleukin-17) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IL-17

  7. TNF-α (Tumor necrosis factor-α) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of TNF-α

  8. TGF-β (Transforming growth factor-β) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of TGF-β

  9. IFN-γ (Interferon-γ) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of IFN-γ

  10. SDF-1 (Stromal cell-derived factor-1) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of SDF-1

  11. CRP (C-reaction protein) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of CRP

  12. MMP-9 (Matrix metalloprotein-9) [ Time Frame: Day 1, Day 2, Day 3, Day 7, Day 28, Day 29, Day 30, Day 31, Day 35, Day 56, Day 57, Day 58, Day 59, Day 64, Day 85, Week 12, Week 20, Week 32, Week 56 ]
    The concentration of MMP-9



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 75 years old (including borderline values) at screening, regardless of gender
  • Diagnosed with decompensated hepatitis B cirrhosis according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 edition)
  • There's no significant reduction in cirrhotic symptoms or no significant improvement in quality of life score after more than 3 months of strict medical conservative treatment
  • HBV DNA ≤ 1000 IU/mL at the time of screening
  • Fully understand the informed consent form, voluntarily subject to the trial and sign the informed consent form.

Exclusion Criteria:

  • other causes of cirrhosis, such as alcoholic hepatitis, viral hepatitis C, autoimmune hepatitis and metabolic-related fatty liver disease
  • Child-Pugh score >12;
  • History of malignancy of the liver or other organs, or a family history of liver malignancy in three generations of immediate family members;
  • Current serious medical conditions that would affect your safety and treatment efficacy assessment as determined by the investigator, such as: Class II or higher abnormal cardiac function (NYHA criteria), cardiovascular disease such as ischemic heart disease (e.g., myocardial infarction or angina), poorly controlled diabetes (fasting glucose ≥ 10 mmol/L or glycated hemoglobin (HbA1c) ≥ 8%), serum creatinine > 2 times the upper limit of normal (ULN), etc;
  • Recent uncontrolled gastrointestinal bleeding (e.g., severe bleeding tendency or active bleeding within 3 months prior to screening, or clinically significant upper gastrointestinal hemorrhage event within 4 weeks prior to screening), as determined by the investigator to be unsuitable for participation in this trial;
  • Have had hepatic encephalopathy or hepatorenal syndrome within 3 months prior to screening
  • Spontaneous peritonitis or a more severe active infection within 2 weeks prior to the trial
  • Positive infectious disease test (serum anti-HIV antibody, anti-HCV antibody, syphilis antibody either positive) or active tuberculosis;
  • Those who have received human albumin within 3 weeks prior to the first infusion of the test drug;
  • Those who have the history of venous thrombosis or pulmonary embolism
  • Drug addicted or alcohol abusers;
  • Women who are pregnant or breastfeeding;
  • Persons with a history of severe drug allergy or hypersensitivity;
  • History of a serious mental disorder, including uncontrolled major depression or controlled or uncontrolled psychosis, within 24 months prior to screening;
  • Those who have participated in other interventional clinical trials within 3 months prior to screening or are participating in other interventional clinical trials, or who have received prior stem cell therapy
  • Those who are proposed for liver transplantation within 3 months;
  • Other conditions that, in the opinion of the investigator, are not suitable for participation in this clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05948982


Contacts
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Contact: Wenli Liu +86 13402137712 liuwenli@xibaozhiliao.cn

Sponsors and Collaborators
Asia Cell Therapeutics (Shanghai) Co., Ltd.
Investigators
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Principal Investigator: Lungen Lu, MD Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
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Responsible Party: Asia Cell Therapeutics (Shanghai) Co., Ltd.
ClinicalTrials.gov Identifier: NCT05948982    
Other Study ID Numbers: QS-UCMSC-DLC
First Posted: July 17, 2023    Key Record Dates
Last Update Posted: July 17, 2023
Last Verified: July 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Asia Cell Therapeutics (Shanghai) Co., Ltd.:
Decompensated hepatitis B cirrhosis
Human Umbilical Cord Mesenchymal Stem Cells
Additional relevant MeSH terms:
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Hepatitis B
Hepatitis
Liver Cirrhosis
Fibrosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections
Pathologic Processes