This study is a randomized, open-label, multicenter phase 2 clinical trial to evaluate the efficacy and safety of AHB-137 injection in participants with CHB treated with Nucleos(t)ide Analogue (NAs).

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Adults ≥18 years of age and up to 65 years of age (inclusive) at Screening who are able to provide informed consent, comply with study procedures, and agree to discontinue nucleos(t)ide analog (NA) therapy if protocol-defined discontinuation criteria are met.
2. Body mass index (BMI) ≤35 kg/m².
3. Documented chronic hepatitis B virus (HBV) infection for ≥6 months prior to randomization, defined by hepatitis B surface antigen (HBsAg) positivity or detectable HBV DNA.
4. Receiving stable, approved nucleos(t)ide analog (NA) monotherapy for ≥6 months prior to randomization.
5. HBV DNA meeting protocol-specified virologic criteria at Screening.
6. Hepatitis B surface antigen (HBsAg) level meeting protocol-specified virologic criteria at Screening.
7. Alanine aminotransferase (ALT) meeting protocol-specified criteria at Screening.
8. Screening electrocardiogram (ECG) without clinically significant abnormalities and with a Fridericia-corrected QT interval (QTcF) ≤450 msec for males or ≤470 msec for females.
9. Females of childbearing potential must not be breastfeeding and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to first dose.
10. Males and female participants of childbearing potential must agree to use protocol-specified effective contraception during the dosing period and for ≥6 months after the last dose of AHB-137.

Exclusion Criteria:

Participants will be excluded from the study if any of the following criteria apply:

1. Clinically significant disease other than chronic hepatitis B virus (HBV) infection.

2. Concomitant clinically significant liver disease.

3. Any severe infection (other than chronic HBV infection) within 1 month prior to randomization.

4. History of immune thrombocytopenia.

5. Current suspected liver cirrhosis and/or evidence of cirrhosis by protocol-specified criteria for FibroScan® or equivalent imaging modality (e.g., ultrasound elastography); historical FibroScan® (or equivalent) results with documentation within 6 months from screening is acceptable.

6. History of liver cirrhosis defined by liver biopsy or by FibroScan® or equivalent imaging modality using protocol-specified criteria.

7. Prior history of, current diagnosis of, or suspected hepatocellular carcinoma (HCC), or alpha-fetoprotein (AFP) ≥20 ng/mL at Screening.

8. History of extrahepatic diseases potentially associated with HBV infection.

9. Laboratory evidence of active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), or active syphilis. Participants with positive HCV or HDV serology and documented negative HCV RNA or HDV RNA, respectively, are eligible.

10. Protocol-specified abnormal laboratory values at Screening.

11. History of vasculitis or presence of signs or symptoms suggestive of vasculitis, or history or presence of diseases associated with vasculitis.

12. History of malignancy within 5 years prior to Screening, except for adequately treated non-melanoma skin cancer. Participants currently undergoing evaluation for potential malignancy are excluded.

13. History of hypersensitivity or allergy to any component of the investigational product (IP).

14. Major trauma or major surgery within 3 months prior to Screening, or planned surgery during the study period unless eligibility is confirmed by the Medical Monitor.

15. Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant compliance.

16. Female participants who are pregnant, breastfeeding, planning pregnancy during the study, or unwilling to refrain from egg donation and/or in vitro fertilization during the study.

17. Participation in another clinical trial or receipt of any investigational product prior to first dose in this study within:

    1. Five half-lives (if known) or twice the duration of biological effect (if known), whichever is longer, or
    2. Six months, if neither half-life nor duration of effect is known

18. Prior treatment with antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies.

19. Any of the following prior or concomitant therapies:

    1. Prolonged use of immunomodulators (e.g., corticosteroids, methotrexate), cytotoxic drugs, or biologics (e.g., monoclonal antibodies) within 6 months prior to first IP administration, except for short-term treatment (≤2 weeks) or topical/inhaled corticosteroids
    2. Interferon therapy within 12 months prior to first dose
    3. Vaccination within 1 month prior to Screening, except for influenza or SARS-CoV-2 (COVID-19) vaccination or booster
    4. Current treatment with bulevirtide

20. Requirement for long-term regular use of anticoagulants (e.g., warfarin, factor Xa inhibitors) or antiplatelet agents (e.g., clopidogrel or regular aspirin), except for low-dose aspirin.

21. Any other condition or circumstance that, in the Investigator's judgment, would make the participant unsuitable for participation in the study.