Chronic hepatitis B
Conditions
Interventions
LD Group:EPI-003T I.V
MD Group:EPI-003T I.V
HD Group:EPI-003T I.V
extension group-1:EPI-003T I.V
Single dose
Sponsors
Shulan (Hangzhou) Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. The age at signing the informed consent form should be between 18 and 70 years old (inclusive). 2. The body mass index (BMI) at screening should be >= 18 kg/m^2 and = 6 months before screening, and the baseline titer being between HBsAg >= 100 and 4000 IU/mL. 4. Before screening, the patient has received a stable dose of NA (entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide) treatment for >= 6 months and plans to continue receiving the same dose during the study. Patients can also take other NAs, but approval from the sponsor is required before participation. 5. HBV DNA is below the detection limit (LLOQ) in at least two consecutive samples taken at intervals of 3 months, and one of them is the test result from the central laboratory during the screening period. 6. At screening, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be <= 1 times the upper limit of normal (ULN). 7. There is no planned pregnancy within one year, and contraceptive measures are taken. The contraceptive methods that can be used are detailed in Appendix 1: Contraceptive Measures, Definition of Reproductive Age Women, and Contraceptive Requirements.
Exclusion criteria
Exclusion criteria: 1. Any participants with evidence of non-HBV causes of liver disease. This includes but is not limited to hepatitis A virus, hepatitis C virus (HCV), hepatitis D virus (HDV) infection or hepatitis E virus (HEV) infection, drug or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, primary biliary cirrhosis, primary sclerosing cholangitis, non-alcoholic fatty liver disease or any other non-HBV liver disease deemed clinically significant by the investigator. 2. Participants who have had or currently have diagnosed liver fibrosis or cirrhosis, with evidence including: - Liver biopsy, or - FibroScan® measurement values greater than 8.6 kPa within 1 year prior to screening. 3. Liver ultrasound or other imaging results suggesting hepatocellular carcinoma (HCC). If the patient has not undergone liver ultrasound within 6 months prior to the first day (with proof of results), a liver ultrasound will be performed to assess for HCC or other abnormalities. 4. Participants with baseline serum alpha-fetoprotein (AFP) > ULN. 5. Positive HIV-1/HIV-2 antibody, syphilis spirochete antibody tests. 6. History of acute febrile illness within 1 week before administration, asymptomatic virus, bacteria (including upper respiratory tract infection) or fungal (non-skin) infection. 7. Received anti-HBV treatment other than NAs within 6 months prior to administration, or planned to use during the study. 8. Any of the following laboratory values at screening (with sponsor approval, PI can repeat screening of laboratory tests once [for values considered incorrect or PI considers clinically insignificant]): - International Normalized Ratio (INR) > 1.2 × ULN, unless the patient's anticoagulation treatment plan is stable, or the investigator considers the value to be clinically insignificant; - Albumin 1.2 × ULN; - Total bilirubin > 1.5× ULN; - Platelets 20 mg/day) before administration; 10. Have a history of myocarditis or pericarditis, or have a known potential risk of myocarditis or pericarditis, any unexplained syncope, syncope attack, arrhythmia, clinically significant ECG abnormalities, QT abnormalities or any known risk factors for torsades de pointes ventricular tachycardia (such as hypokalemia, heart failure) at screening. At screening, 3 ECGs should be continuously recorded. If in at least 2 of the ECGs, male patients have QTcF > 450 milliseconds, or female patients have QTcF > 470 milliseconds, the patient must be excluded; 11. History of anaphylactic shock or severe drug allergy; 12. History of thrombotic disease or positive factor V Leiden factor and/or prothrombin 20210 mutation gene testing; 13. Known or suspected intolerance or allergy to the components of the study drug or closely related compounds or any of their components; 14. Received any investigational drug within 30 days before administration or within
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence rate of adverse events;Physical examination;Laboratory tests (including blood routine, blood biochemistry, urine routine, coagulation function, thyroid function, etc.); Vital signs;12-lead electrocardiogram; | — |
Secondary
| Measure | Time frame |
|---|---|
| Optimal Active Dose (OBD);Extended Recommended Dose (RED);HBsAg & HBsAb & HBV-DNA Titer;The time required from the first administration of the drug until HBsAg is cleared, HBeAg is cleared (only for patients with positive HBeAg at baseline), HBsAb seroconversion and HBeAb seroconversion (only for patients with negative HBeAb at baseline);The pharmacokinetic (PK) parameters of cationic lipid nanoparticles LNP (plasma) and mRNA expression levels (whole blood);The positive rate of anti-PEG antibodies;HBsAg loss and HBsAb seroconversion;HBeAg loss and HBeAb seroconversion (Only for patients with negative HBeAb at the baseline); | — |
Countries
China
Contacts
Public ContactLingling Tang & Lihua Wu
Shulan (Hangzhou) Hospital
Outcome results
None listed