Hepatitis B, Chronic
Conditions
Brief summary
AB-10-8003 is a randomized, multi-center phase II study to evaluate the efficacy and safety of AHB-137 in subjects with HBeAg-negative CHB under stable NA treatment.
Detailed description
The study is to evaluate the efficacy and safety of AHB-137 in HBeAg-negative CHB subjects. The total duration of the study, including screening phase, treatment phase and follow-up phase.
Interventions
DRUGAHB-137
AHB-137 injection will be administered subcutaneously.
DRUGAHB-137 and Placebo
AHB-137and placebo will be administered subcutaneously.
DRUGAHB-137 (16weeks)
AHB-137 injection will be administered subcutaneously.
Sponsors
Ausper Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants voluntarily participate in the study, and sign the Informed Consent Form (ICF) prior to screening, able to complete the study and discontinue their NA therapy according to the protocol; 2. At least 18 years old at the time of signing of the informed consent; 3. Body Mass Index (BMI) between 18 to 32 kg/m\^2(inclusive) ; 4. Participants who are Hepatitis B envelop antigen (HBeAg) negative during screening; 5. Participants whose serum HBsAg positive for at least 6 months prior to screening; 6. Participants who have stable on NA therapy at least 6 months prior to screening; 7. Participants with HBsAg concentration \>100 IU/mL and≤3000 IU/mL, HBV DNA\<100 IU/mL; 8. Participants with alanine aminotransferase (ALT)≤ 2x upper limit of normal (ULN); 9. For women of childbearing potential, she should be non-pregnant or non-lactating during screening, and participants (and partners) are willing to take effective contraceptive measures from the screening until the last visit or at least 6 months after the last dosing.
Exclusion criteria
1. Clinical significant abnormalities except Chronic HBV infection, such as acute coronary syndrome within 6 months before screening, evidence of major surgery, major or unstable heart disease, bleeding tendency or significant coagulation disorder within 3 months before screening; 2. Any clinically significant liver diseases, including but not limited to hepatitis caused by other pathogenic infections, hemochromatosis, Wilson disease, primary biliary cirrhosis, autoimmune liver diseases, alcoholic liver disease, severe non-alcoholic fatty liver disease, Drug-induced liver injury, etc.; 3. Participants with severe infection requiring intravenous anti-infection treatment 1 month before randomization; 4. Active hepatitis C, Human immunodeficiency virus (HIV) positive, syphilis positive; 5. Liver stiffness measurement (LSM) \> 9.0 kPa when screening; 6. Diagnosed or suspected hepatocellular carcinoma; 7. The laboratory examination results are obviously abnormal; 8. History of vasculitis or signs and symptoms of potential vasculitis; 9. History of extrahepatic disease that may be related to HBV immune status; 10. Administration of immunosuppressants within 3 months prior to screening, except for short-term use (≤2 weeks) or topical/inhaled steroids. Administration of immunomodulators (thymosin) and cytotoxic drugs within 6 months prior to the first study intervention or have a history of vaccination within 1 month prior to screening or planned administration during the study. 11. Administration of any Interferon within 6 months prior to screening; 12. History of malignant tumor within the past 5 years; 13. Any suspicion of drug component allergy, or allergic constitution (various drug and food allergy, and judged by the investigator to be clinically significant) in participants; 14. Participants who have significant trauma or major surgery within 3 months before screening, or plan to perform surgery during the study; 15. Blood donation or blood loss more than 400 mL within 12 weeks before screening; Blood transfusion; Blood donation or blood loss not less than 200 mL within 1 month before screening; 16. Concurrently participating in another clinical study, or received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the study treatment or 90 days; 17. Any oligonucleotide or siRNA treatments within 12 months prior to first dosing; 18. Any other circumstances or conditions for which the investigator considers that the participants are inappropriate to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants achieving HBsAg < limit of detection (LOD) 0.05 International Unit/mL (IU/mL) and HBV DNA < lower limit of quantitation (LLOQ) with or without anti-HBs seroconversion at the end of treatment. | Up to 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving HBsAg lower than LOD and HBV DNA lower than LLOQ , regardless of whether HBsAg seroconversion is observed | At 8 weeks | — |
| Proportion of participants meeting NA treatment discontinuation criteria. | Up to 48 weeks | — |
| Changes of the score of hepatitis B quality of life instrument (HBQOL) compared with baseline | Up to 72 weeks | This scale has 31 items, including 7 dimensions: psychological status, expected anxiety, vitality, shame, infectivity, health vulnerability, and viral response. Each item is scored on a 5-point scale, with higher scores indicating a more severe impact of hepatitis B on quality of life. |
| Percentage of participants with different levels of HBsAg reduction compared with baseline | Up to 72 weeks | — |
| Serum levels of HBV DNA, HBsAg, highly sensitive HBsAg, HBcrAg, HBV RNA, HBsAb, HBeAb and HBsAg-HBsAb. | Up to 72 weeks | — |
| The time from the discontinuation of NA treatment to virological relapse | Up to 72 weeks | — |
| Sequencing of the Viral DNA and/or viral RNA analysis for detection of drug resistance of AHB-137 | Up to 24 weeks | — |
| The time from the discontinuation of NA treatment to clinical relapse | Up to 72 weeks | — |
| Immunogenicity: number and percentage of participants with detectable anti-drug antibodies (ADA) | Up to 72 weeks | — |
| Changes of cytokine levels compared with baseline | Up to 72 weeks | — |
| The pharmacokinetic profile of AHB-137: Maximum concentration (Cmax) of AHB-137 in plasma | Up to 72 weeks | — |
| The pharmacokinetic profile of AHB-137: Area under the concentration-time curve (AUC) of AHB-137 | Up to 72 weeks | — |
| Plasma concentrations of AHB-137 | Up to 72 weeks | — |
| Proportion of participants maintaining sustained response. | Up to 72 weeks | — |
| Safety: number of participants with adverse events (TEAEs), serious adverse events (SAE) and clinically significant examination results, including laboratory examination, electrocardiogram (ECG) examination, physical examination and vital signs | Up to 72 weeks | — |
Countries
China
Outcome results
None listed