Acute-on-chronic liver failure
Conditions
Interventions
0.5mg:0.5mg/Kg, single administration, after 20 days of elution, enter continuous administration, once a week, for 4 consecutive weeks.
1.0mg:1.0mg/Kg, single administration, after 20 days of elution, enter continuous administration, once a week, for 4 consecutive weeks.
Test group:0.5mg/Kg or 1.0mg/Kg, intravenous drip, continuous administration
placebo group:0.5mg/Kg or 1.0mg/Kg, intravenous drip, continuous administration
Sponsors
Shenzhen Third People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Phase IIa - Main Inclusion Criteria (1) The age range for signing the informed consent form is between 18 and 75 years old (including the threshold); (2) According to the "Diagnosis and Treatment Guidelines for Liver Failure (2018 Edition)" issued by the Liver Failure and Artificial Liver Group of the Infectious Diseases Branch of the Chinese Medical Association and the Severe Liver Disease and Artificial Liver Group of the Hepatology Branch of the Chinese Medical Association, it has been diagnosed with chronic acute liver failure, with specific indicators including: a) Patients with chronic liver disease (chronic hepatitis B, autoimmune hepatitis, drug-induced hepatitis, etc.) and the acute attack factor is drugs; b) Serum TBil = 10 × ULN or average daily increase = 17.1 µ mol/L; c) Meet any of the following three criteria: A has a tendency to bleed, PTA = 40% (or INR = 1.5); B combined with hepatic encephalopathy; C combined with hepatorenal syndrome or ascites. (3) Screening was conducted in the early stage of liver failure and did not meet the criteria for liver transplantation; Early manifestations of liver failure: Extreme fatigue, accompanied by severe gastrointestinal symptoms such as anorexia, vomiting, and bloating; ALT and/or AST continue to significantly increase, and jaundice progressively deepens (TBil>171 µ mol/L or daily increase>17.1 µ mol/L); Bleeding tendency, 30%171 µ mol/L or daily increase>17.1 µ mol/L); Bleeding tendency, 30%<PTA = 40% (or 1.5 = INR<1.9); No complications or other extrahepatic organ failure. Mid stage
Exclusion criteria
Exclusion criteria: Phase IIa - Main exclusion criteria (1) Patients with a history of allergies or severe allergies to protein drugs (CTCAE v5.0 score>grade 3); (2) Patients who have completed liver transplantation or plan to undergo liver transplantation within one month. (3) ACLF patients in the middle and late stages; (4) Severe grade III ascites or refractory ascites accompanied by stage III-IV hepatic encephalopathy. (5) Individuals who have received artificial liver treatment within one week prior to screening. (6) Individuals with malignant tumors or a history of malignant tumors in the past; Patients with lung cancer, liver cancer, pancreatic cancer, gastrointestinal tract and other tumors were diagnosed by imaging (ultrasound, CT or MRI) and tumor markers (AFP, CEA, CA125 or CA199, etc.) during the screening period or within one month before the screening period. (7) Individuals who have undergone gastroscopy or imaging (abdominal B-ultrasound, CT, or MRI) during the screening period or within one month prior to screening, and whose results indicate a risk of severe varicose veins with bleeding. (8) Subjects with acute kidney injury (AKI) defined by KDIGO criteria: (1) Scr elevation = 26.5 µ mol/L (0.3mg/dL, 1mg/dL=88.4 µ mol/L) within 48 hours; (2) Scr increases by 1.5 times or more than the baseline value within 7 days; (3) Decreased urine output (1.9 or PTA1.5 × ULN. (10) Patients with severe respiratory dysfunction, difficulty breathing, or failure. (11) Severe infections that cannot be controlled by concomitant medications, including infections of major organs such as the abdominal cavity, lungs, urinary tract, and skin. (12) HIV positive individuals, or active tuberculosis or syphilis infected individuals. (13) Individuals with a history of unstable ischemic heart disease, congestive heart failure, myocardial infarction, stroke, severe arrhythmia, etc. (14) Subjects with uncontrolled severe hypertension or diabetes. (15) Pregnant or lactating women, or those who test positive for pregnancy. (16) Participants in clinical trials of other drugs or medical devices within 30 days prior to randomization or within five drug half lives. (17) Having undergone trauma or major surgery (e.g. requiring general anesthesia) within 28 days prior to the first administration of the investigational drug. Note: Participants who plan to undergo surgical procedures under local anesthesia are eligible to participate in the study. (18) Any serious underlying medical or mental condition (such as alcohol or drug abuse), dementia, or change in mental state; Or any issues that may impair the subject's ability to receive or tolerate planned treatment at the research center, understand informed consent, or issues that the researcher deems taboo to participate in the study or confound the evaluation or study results specified in the protocol. (19) Researchers believe that other conditions are not suitable for participating in this study. Phase IIb - Main exclusion criteria If one of the following conditions is met, the subject is not suitable for inclusion in this study. (1) Patients with a history of allergies or severe allergies to protein drugs (CTCAE v5.0 score>grade 3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events and serious adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics parameters;Immunogenicity;Tumor necrosis factor related apoptosis inducing ligand concentration;Model for End-Stage Liver Disease score;survival rate;cure rate;improvement rate;Asian Pacific Association for the Study of the Liver ACLF Research Consortium Score; | — |
Countries
China
Contacts
Public Contactjun chen
Shenzhen Third People's Hospital
Outcome results
None listed