Chronic hepatitis B
Conditions
Interventions
Healthy participants:Five dose escalation groups, administered via subcutaneous injection
CHB participants:Four groups: the first three groups for dose escalation, and the fourth group at the same dose as the third group, with administration via subcutaneous injection
Sponsors
The First Hospital of Jilin University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: The following inclusion criteria apply to healthy participants (SAD section) : Be able to correctly understand and sign the informed consent form in person. 2. Male or female participants, aged 18 to 55 years old (including the critical value); 3. The body mass index (BMI) should be within the range of 18 to 28 kilograms per square meter (kg/m ²) (including the critical value), with a minimum of 50 kilograms for men and 45 kilograms for women. 4. During the screening period, normal or abnormal clinical laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine), thyroid function, 12-lead electrocardiogram, abdominal ultrasound, frontal chest X-ray, etc. have no clinical significance. 5. For fertile female participants: They must not be pregnant, not in the lactation period, and agree to efficient contraception during the study period; 6. For male participants with fertility: Agree to use efficient contraception during the study period to ensure that their sexual partners are effectively contraceptive. The following inclusion criteria apply to CHB participants (MAD section) : Be able to correctly understand and sign the informed consent form in person. 2. Male or female participants, aged 18 to 65 years old (inclusive of the critical value); 3. The body mass index (BMI) should be within the range of 18 to 32 kilograms per square meter (kg/m ²) (including the critical value), with a minimum of 50 kilograms for men and 45 kilograms for women. 4. Recorded hepatitis B virus infection at >= 6 months before screening: positive HBsAg and/or positive HBV DNA; 5. Negative HBeAg during the screening period; 6. Take the approved first-line oral nucleoside (acid) analogues (NAs) for stable treatment for = 6 months before screening, and take the same NAs stably for at least 3 months before screening. 7. HBV DNA<100 IU/mL during the screening period; 8. The HBsAg level during the screening period should be less than or equal to 1000 IU/mL (applicable to the first three groups in the MAD section, 150mg, 300mg, and 450mg); 9. During the screening period, 1000 IU/mL < HBsAg level = 3000 IU/mL (applicable to Group 4 of the MAD section, 450mg); 10. Serum alanine aminotransferase (ALT) = 2 times the upper limit of the reference value (ULN); The results of transient liver elastography (FibroScan) showed that the liver stiffness measurement (LSM) level was less than 12.4 kPa. Or liver tissue biopsy within 24 months prior to screening shows a Metavir score of F0-F2; 12. For fertile female participants: They must not be pregnant, not in the lactation period, and agree to efficient contraception during the study period; 13. For male participants with fertility: Agree to use efficient contraception during the study period to ensure that their sexual partners are effectively contraceptive.
Exclusion criteria
Exclusion criteria: The following exclusion criteria apply to healthy participants (SAD section) : Those who have hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or syphilis, or have been previously diagnosed with hepatitis A, hepatitis D or hepatitis E and have not been cured; 2. Those who suffer from serious diseases, including but not limited to diseases of the nervous system, cardiovascular system, blood and lymphatic system, immune system, kidneys, liver, thyroid, gastrointestinal tract, respiratory system, metabolism and bones, as well as a history of malignant tumors, and who are determined by the researcher to possibly affect their safety or the research results; 3. Those who suffer from severe mental illness or uncontrolled mental disorders, including but not limited to schizophrenia, bipolar disorder or depression, and whom the researchers consider unsuitable to participate in this clinical trial; 4. The QT/QTc interval is prolonged during screening, such as repeated checks confirming that QTcF is greater than 450 ms (Fridericia formula correction); 5. Participants have risk factors for TdP (such as heart failure, hypokalemia, hypomagnesemia, long or risky bundle branch block, etc.); 6. At the time of screening, if the systolic blood pressure is greater than or equal to 140 mmHg or the diastolic blood pressure is greater than or equal to 90 mmHg, and the researcher assesses that the participant is not suitable for this study; 7. During screening, the creatinine clearance rate (CLcr) calculated by the Cockcroft-Gault formula was <= 80 mL/min; 8. Those who have received a vaccine or a live attenuated vaccine within one month before administration, or plan to receive a vaccine during the trial period; 9. Those who have undergone major surgery in the six months prior to screening or plan to undergo surgery during the study period; 10. Those who have had severe infections or external injuries within 4 weeks prior to screening; 11. Those who have lost no less than 200 milliliters of blood due to non-physiological reasons within one month before administration (including trauma, blood collection, and blood donation), or who plan to donate blood during the trial period or within 30 days after administration; 12. Those with severe allergic constitutions (allergic to two or more drugs and foods), or those who are clearly allergic to the ingredients of this product or its preparations, are determined by the researcher to be unsuitable to participate in this researcher. 13. Those who have a history of severe intolerance to subcutaneous injections (mild reactions such as local swelling or redness are allowed); 14. Abnormalities of abdominal skin, such as tattoos and active skin diseases (inflammation, rashes, etc.), which researchers believe may interfere with the subcutaneous administration of the investigational drug and/or the observation of the reaction at the injection site; 15. Those who have taken any prescription drugs, Chinese herbal medicines or over-the-counter drugs within 14 days before the administration of the investigational drug; 16. The time of participating in clinical trials of other drugs is within 3 months from the treatment of this study, or within 5 half-lives of other trial drugs, or within 6 months before screening for siRNA or antisense oligonucleotide drug clinical trials (if a participant withdraws from the study before treatment, that is, has not received treatment with the study drug, they ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with AEs, SAEs and laboratory abnormalities.; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters;Anti hepatitis B virus parameters;Immunopharmacodynamic parameters;Immunogenicity parameters; | — |
Countries
China
Contacts
Public ContactYanhua Ding;Junqi Niu
The First Hospital of Jilin University
Outcome results
None listed