Chronic Hepatitis B Virus
Conditions
Interventions
Experimental group:LW231
Sponsors
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: Phase Ib: 1. Sign the informed consent form before the study and agree to complete the study according to the protocol requirements; 2. Male or female aged 18-60 years (inclusive); 3. Chronic HBV infection, including (HBsAg or HBV DNA positive for at least 6 months, or a medical history confirming HBV infection for more than 6 months); 4. Eligible if meeting one of the following conditions: (1) Not treated with antiviral therapy; (2) Previously treated with NAs but discontinued before screening, must have stopped medication for 6 months or more by the time of screening; (3) Has been continuously treated with nucleoside analogues (Entecavir [ETV], Tenofovir Disoproxil Fumarate [TDF], Tenofovir Alafenamide [TAF], or Tenofovir Amibufenamide [TMF]) for more than 12 months (with less than 1 month interruption in the past year), and is still receiving treatment at the time of screening, has maintained the same NA treatment for more than 12 months before screening, and agrees not to change this stable regimen throughout the study; 5. LLOQ < HBV DNA = 20,000 IU/ml (equivalent to 10^5 copies/ml); 6. 100 IU/mL < HBsAg < 10,000 IU/ml; 7. Subjects are willing to avoid conception, sperm donation, or egg donation from the date of signing the informed consent form until 3 months after the last dose. Effective non-drug contraception must be used with partners of childbearing potential, as detailed in Appendix 3. Phase II: 1. Sign the informed consent form before the study and be able to complete the study according to the protocol requirements; 2. Male or female aged 18-70 years (inclusive); 3. Chronic HBV infection, including (HBsAg or HBV DNA positive for at least 6 months, or a medical history confirming HBV infection for more than 6 months); 4. Has been continuously treated with nucleoside analogues (Entecavir [ETV], Tenofovir Disoproxil Fumarate [TDF], Tenofovir Alafenamide [TAF], or Tenofovir Amibufenamide [TMF]) for more than 12 months (with less than 1 month interruption in the past year), is still receiving treatment at the time of screening, has maintained the same NA treatment for more than 12 months before screening, and agrees not to change this stable regimen throughout the study; 5. 100 IU/mL < HBsAg < 3,000 IU/ml; 6. HBV DNA < LLOQ or < 20 IU/mL at screening (PCR method); 7. Subjects are willing to avoid conception, sperm donation, or egg donation from the date of signing the informed consent form until 6 months after the last dose. Effective non-drug contraception must be used with partners of childbearing potential, as detailed in Appendix 3.
Exclusion criteria
Exclusion criteria: Ib Phase: 1. Pregnant or breastfeeding women; 2. Continuous alcohol consumption within 6 months before screening (i.e., more than 14 units of alcohol per week: 1 unit = approximately 285 mL of beer with 3.5% alcohol, or 25 mL of liquor with 40% alcohol, or 100 mL of wine with 10% alcohol); 3. Use of cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 28 days before screening; 4. Systemic use of immunosuppressants, immunomodulators (interferons must be discontinued for more than 12 months), or cytotoxic drugs within 6 months before screening; 5. Subjects who received live attenuated vaccines within 1 month before screening, inactivated vaccines within 7 days, or are scheduled for vaccination during the study period; 6. HIV antigen/antibody positive, syphilis treponemal antibody positive and rapid plasma reagin (RPR) positive; 7. Co-infection with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV) (Note: subjects who are HCV antibody positive but HCV RNA negative and HEV IgM positive but HEV RNA negative are excluded); 8. History of chronic liver disease not caused by HBV, such as alcoholic liver disease, autoimmune liver disease, genetic liver disease, metabolic dysfunction-associated fatty liver disease, etc. (excluding simple fatty liver); 9. Progressive liver fibrosis or cirrhosis detected at screening, with liver stiffness measurement (FibroScan) results >=9 kPa; 10. History of hepatocellular carcinoma (HCC), or potential risk for HCC, such as imaging-suspected nodules or abnormal AFP (AFP > upper limit of normal [ULN]), which must be ruled out before enrollment. 10. Previous history of hepatocellular carcinoma (HCC); or may be at risk of hepatocellular carcinoma, such as: suspicious nodules or abnormal AFP on imaging (AFP>upper limit of normal range [ULN]), which should be ruled out before enrollment; 11. Presence of active infection (non-infectious disease), or medical history: Systemic systemic anti-infective therapy within 4 weeks prior to randomization; Sore throat, nasal congestion, acute upper respiratory tract infection, or systemic acute infection within 2 weeks prior to randomization; Presence of recurrent, chronic or other active infections at screening, which may increase the risk to the subject as judged by the investigator's assessment; 12. Currently receiving nephrotoxic drugs or drugs that can alter renal excretion; 13. Abnormal hematological and biochemical parameters, including: (1) Platelets3×ULN; (4) Total bilirubin >1.3×ULN or direct bilirubin >1.3×ULN; (5) Albumin1.3×ULN; (7) Glomerular filtration rate<=60 mL/min/1.73 m^2 (calculated by CKD-MDRD formula) 14. Any type of active malignant tumor or history of malignancy (basal cell carcinoma of the skin that has been in complete remission for 5 years or more without any signs of recurrence after radical treatment, except cervical cancer in situ and papillary thyroid carcinoma); 15. Cardiovascular and cerebrovascular abnormalities (any of the following are excluded): (1) Those who have a history of consciousness disorder or unexplained coma in the past 12 months; (2) Class II to IV heart failure as defined by the New York Heart Association. Myocardial infarction or arterial thrombotic event, unstable arrhythmia, or unstable angina within the past 12 months; (3) Cerebrovascular accident or acute congestive heart fail
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib dose-limiting toxicity (DLT), incidence and severity of adverse events in different groups, laboratory test parameters, vital signs and other safety parameters in different groups.;Phase II HBsAg; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters and characteristics after multiple administrations in different dose groups of Phase Ib;Phase Ib: Hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis B surface antigen (HBsAg), serum HBV pregenomic ribonucleic acid (HBV pgRNA), hepatitis B core-related antigen (HBcrAg);Cytokines and cGAS?STING pathway?related genes in Phase Ib;Phase II adverse events, vital signs, and other safety parameters.;Phase II pharmacokinetics;HBsAg, HBeAg, HBcrAg, HBV pgRNA, and the number and percentage of subjects with HBV drug-resistant gene mutations.;Phase II: cytokines, detection of cGAS-STING pathway-related genes, and intrahepatic cccDNA; | — |
Countries
China
Contacts
Public ContactYunqing Qiu
Affiliated hangzhou first people's hospital, zhejiang university school of medicine
Outcome results
None listed