Decompensated Hepatitis B Cirrhosis
Conditions
Keywords
UC-MSCs, decompensated hepatitis B cirrhosis
Brief summary
Phase I (Single Administration, Randomized, Double-blind, Dose Escalation)Primary Objective: To evaluate the safety and tolerability of Human Umbilical Cord Mesenchymal Stem Cell Injection in patients with decompensated hepatitis B cirrhosis, and to determine the safe clinical dose.Secondary Objective: To evaluate the preliminary efficacy of Human Umbilical Cord Mesenchymal Stem Cell Injection in patients with decompensated hepatitis B cirrhosis, providing a basis for the design of subsequent clinical trial protocols.Exploratory Objective: To evaluate the pharmacokinetic characteristics and immunogenicity of Human Umbilical Cord Mesenchymal Stem Cell Injection in patients with decompensated hepatitis B cirrhosis.Phase II (Multiple Administrations, Randomized, Double-blind, Dose Expansion)Primary Objective: To evaluate the preliminary efficacy of Human Umbilical Cord Mesenchymal Stem Cell Injection in patients with decompensated hepatitis B cirrhosis.Secondary Objective: To evaluate the safety of Human Umbilical Cord Mesenchymal Stem Cell Injection in patients with decompensated hepatitis B cirrhosis.Exploratory Objective: To evaluate the pharmacokinetic characteristics and immunogenicity of Human Umbilical Cord Mesenchymal Stem Cell Injection in patients with decompensated hepatitis B cirrhosis.
Interventions
venous reinfusion
Sponsors
Beijing Tuohua Weiye Biotechnology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged between 18 and 75 years (inclusive) at screening, regardless of gender. * Diagnosed with decompensated hepatitis B cirrhosis with a history of portal hypertension-related complications according to the Guidelines for the Diagnosis and Treatment of Cirrhosis (2019 Edition). * After at least 3 months of strict conservative medical treatment (including antiviral therapy with nucleos(t)ide analogues, hepatoprotective, symptomatic, and nutritional support therapy), there has been no significant alleviation of cirrhosis symptoms or improvement in quality of life scores, and the investigator deems the subject suitable for stem cell therapy. * HBV DNA level \< 2 × 10³ IU/mL at screening. * Not suitable for liver transplantation, or lacking a liver donor source. * Both the subject and their partner have no plans for pregnancy from screening until 6 months after the end of the trial and agree to use effective non-pharmacological contraception during the trial period. * Fully understand the informed consent form, voluntarily participate in the trial, and sign the informed consent form.
Exclusion criteria
* Cirrhosis due to other causes, such as alcoholic hepatitis, hepatitis C virus infection, autoimmune hepatitis, and metabolic dysfunction-associated steatotic liver disease (MASLD). * Child-Pugh score \> 12 points. * History of malignancy in the liver or other organs, or a family history of liver malignancy in first-degree relatives. * The investigator judges that the subject currently has severe internal medical diseases that would affect the safety and efficacy evaluation of the treatment, such as: cardiovascular diseases including cardiac function abnormality of Class III or above (according to NYHA criteria), ischemic heart disease (e.g., myocardial infarction or unstable angina), poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L or glycosylated 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 major upper gastrointestinal bleeding event within 4 weeks prior to screening), deemed unsuitable for the trial by the investigator. * Occurrence of hepatic encephalopathy or hepatorenal syndrome within 3 months prior to screening. * Presence of spontaneous bacterial peritonitis or severe active infection within 2 weeks prior to screening. * Positive results in infectious disease serology (positive for serum anti-HIV antibody, anti-HCV antibody, or syphilis antibody) or patients with active tuberculosis. * Use of human albumin within 3 weeks prior to the first infusion of the investigational product. * History of venous thrombosis or pulmonary embolism, deemed unsuitable for the trial by the investigator. * Drug addiction or alcohol abuse. * Pregnant or lactating women. * Allergy to any component of the umbilical cord mesenchymal stem cells or excipients, or history of severe drug allergy or allergic constitution. * History of severe psychiatric disorders within 24 months prior to screening, including uncontrolled severe depression or controlled/uncontrolled psychosis. * Participation in other interventional clinical trials within 3 months prior to screening or currently, or previous receipt of stem cell therapy. * Planned liver transplantation within 3 months after screening. * Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and characteristics of any adverse events and serious adverse events associated with human umbilical cord mesenchymal stem cell injection therapy | within 28 days after administration | Safety Indicator |
| Determine the recommended dose for phase II（RP2D） | Periprocedural | Safety Indicator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Model for End-stage Liver Disease score from baseline | Week 1, week 2, week 4, week 8, week 12, week 24, week 36, week 52 after administration | The calculated baseline score is 6 points. The 40-point mark is an upper limit set in clinical application, used to indicate an extremely high risk of mortality and to guide the most urgent allocation of liver transplants. Efficacy Endpoint |
| Child-Pugh score change from baseline | Week 1, week 2, week 4, week 8, week 12, week 24, week 36, week 52 after administration | The theoretical minimum score of the Child-Pugh classification is 5 points, and the maximum is 15 points. A higher score indicates poorer liver reserve function and a less optimistic prognosis for the patient Efficacy Endpoint |
| Hepatic hardness changes from baseline | Week 24, week 52 after administration | Efficacy Endpoint |
| Spleen hardness changes from baseline | Week 24, week 52 after administration | Efficacy Endpoint |
| Change in Liver Function Indicators from Baseline: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Bilirubin (TBIL), Gamma-Glutamyl Transferase (γ-GGT), Alkaline Phosphatase (ALP), Albumin (ALB), Cholinesterase (CHE) | Week 1, week 2, week 4, week 8, week 12, week 24, week 36, week 52 after administration | Efficacy Endpoint |
| Change in International Normalized Ratio from Baseline | Week 1, week 2, week 4, week 8, week 12, week 24, week 36, week 52 after administration | Efficacy Endpoint |
| Prothrombin Time from Baseline | Week 1, week 2, week 4, week 8, week 12, week 24, week 36, week 52 after administration | Efficacy Endpoint |
| Prothrombin Activity from Baseline | Week 1, week 2, week 4, week 8, week 12, week 24, week 36, week 52 after administration | Efficacy Endpoint |
| Change in HBV DNA from Baseline | Week 1, week 2, week 8, week 24, week 36, week 52 after administration | Efficacy Endpoint |
| Liver transplant-free survival | Periprocedural | Efficacy Endpoint |
| The incidence of complications related to decompensated cirrhosis (the following complications were calculated separately: esophageal and gastric varices bleeding, sepsis, hepatic encephalopathy, hepatorenal syndrome) | Periprocedural | Efficacy Endpoint and Safety Indicator |
| Incidence and Characteristics of Any Treatment-Related Adverse Events and Serious Adverse Events Associated with Human Umbilical Cord Mesenchymal Stem Cell Injection Therapy | Week 5 to week 52 after administration | Safety Indicator |
Countries
China
Contacts
CONTACTShi Cheng
Outcome results
None listed