An exploratory clinical trial to evaluate the safety and efficacy of TDI01 suspension in the patients with hepatic fibrosis
Phase 1
Recruiting
- Conditions
- Hepatic fibrosis
- Registration Number
- ChiCTR2400082056
- Lead Sponsor
- West China Hospital, Sichuan University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Be able to understand and follow protocol requirements, voluntarily participate in trials and sign a written ICF;<br>2. Adult male or female subjects between 18 and 70 years of age (including 18 and 70 years of age, based on the date of signing the informed consent) (including the boundary);<br>3. At the time of screening, the weight of male subjects should be no less than 50 kg, the weight of female subjects should be no less than 45 kg, and the body mass index [BMI= weight (kg)/height^2 (m^2)] should be in the range of 18.0~30.0kg/m^2 (including boundary values);<br>4. The disease was caused by hepatitis B liver fibrosis, non-alcoholic liver fibrosis and immune liver fibrosis, and the pathological diagnosis results within 6 months showed chronic liver fibrosis grade F1-F4;<br>5. The Child-Pugh score for liver function is 5-6 points;<br>6. Have the safe puncture path of percutaneous liver biopsy, and agree to liver biopsy;<br>7. No severe coagulopathy or bleeding disorder (e.g. hemophilia);<br>8. Male subjects and their partners or female subjects must agree to use one or more effective contraceptive methods for at least 90 days after signing the ICF and no fertility, sperm or egg donation plans for at least 90 days after the last medication.
Exclusion Criteria
- During screening, imaging indicated malignant hepatic placeholders or patients with alpha-fetoprotein (AFP) levels higher than 50 ng/ml;<br>2. A history of clinically significant drug allergy or allergic disease (such as asthma, urticaria, eczema dermatitis, etc.), or a probable or clear allergy to the investigational drug (including angiotensin receptor enkeenase inhibitors, angiotensin receptor antagonists, and renin inhibitors) and any excipients thereof as determined by the investigator;<br>3. Patients with decompensated cirrhosis: ascites, hepatic encephalopathy, esophageal and gastric varices rupture bleeding and other complications of decompensated cirrhosis;<br>4. Drug induced liver injury; Acute liver injury caused by various reasons; Patients with hepatorenal syndrome; Severe abdominal effusion or pleural effusion requiring puncture drainage; Patients with severe portal hypertension or previous portal shunt surgery; Patients with primary biliary cholangitis, biliary obstruction, cholestatic liver disease and other diseases affecting bile excretion; hemoglobin 80g/L;<br>5. Combined with drug-induced liver injury or hereditary liver disease;<br>6. Patients preparing for a liver transplant or who have had a liver transplant in the past;<br>7. Severe heart disease (including, but not limited to, unstable ischemic heart disease, New York Heart Association Class III/IV congestive heart failure, or acute myocardial infarction) or concomitant uncontrolled or severe arrhythmias, such as long QT syndrome, ventricular tachycardia, etc., in the 3 months prior to screening;<br>8. The researchers determined that there were other diseases or histories that were clinically significant or might prevent subjects from following and completing the study, including the central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, blood system, immune system, psychiatry, metabolic abnormalities, gastrointestinal surgery, etc.;<br>9. History of lymphoproliferative disease or any known history of malignancy within 5 years prior to screening (other than treated basal cell carcinoma or actinic keratosis, carcinoma in situ of the cervix, or resectomized nonaggressive malignant colon polyps);<br>10. Patients who received anticoagulant or antiplatelet drugs within 7 days before the first dose;<br>11. Patients, except those with autoimmune liver fibrosis, who have received immunomodulators (including but not limited to interferon (PEGylated or non-pegylated interferon) and thymosin) for more than 2 weeks within 6 months before the first dose;<br>12. Patients with continuous and regular use of anti-fibrosis drugs (including but not limited to: compound Biejia Ruangan tablets/capsules, Fuzheng Huayu tablets/capsules, Anluo Huayxian pills) for more than 3 months before the first administratio;<br>13. Any of the test indicators during screening or before randomization meet the following criteria: a) Serum aspartate aminotransferase (AST), or serum alanine aminotransferase (ALT) >=5.0×ULN (upper limit of normal); TBIL>=5.0×ULN (upper limit of normal); b) Platelet (PLT) counts < 70×10^9/L or severe active bleeding (except when platelet levels judged stable by the investigator) or prothrombin time (PT) prolongation >=3s, or International normalized ratio (INR) > 1.5, or other contraindications for liver histopathologic examination;<br>14. Human immunodeficiency virus antibody (HIV Ab) positive, serum treponema pallidum antibody (TP Ab) positive;<br>15. A history
Study & Design
- Study Type
- Interventional study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method All adverse events;Serious Adverse Events;Incidence and severity of adverse events and abnormal clinical laboratory indicators during treatment;Liver fibrosis improvement rate at 24 weeks;Proportion of subjects with 24 week liver fibrosis Batts-Luding score that had decreased by >=1 point or more compared with pre-treatment;
- Secondary Outcome Measures
Name Time Method Proportion of subjects with liver fibrosis Ishak decreased by =1 point or more at 24 weeks compared with before treatment;Proportion of decrease in liver hardness determination (LSM) (kPa) values compared to pre-treatment values at 24 weeks with instantaneous elastic ultrasound imaging (TE) of the liver;Percentage of patients with liver hardness > 30% lower than before treatment on instantaneous elastic imaging at 24 weeks;Collagen proportional area (CPA) at 24 weeks improved the proportion of subjects compared with before treatment;