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 HBeAg-negative 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 (or per local age of majority) and ≤65 years of age 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. Hepatitis B e antigen (HBeAg) negative at Screening.
5. Receiving stable, approved nucleos(t)ide analog (NA) monotherapy for ≥6 months prior to randomization.
6. HBV DNA below the lower limit of quantification (LLOQ) at Screening.
7. Hepatitis B surface antigen (HBsAg) level >100 IU/mL and ≤3,000 IU/mL at Screening.
8. Alanine aminotransferase (ALT) ≤2 × upper limit of normal (ULN) at Screening.
9. Screening electrocardiogram (ECG) without clinically significant abnormalities and with a Fridericia-corrected QT interval (QTcF) ≤450 msec for males or ≤470 msec for females.
10. 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.
11. Male 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, as documented in medical history or identified on physical examination, including but not limited to acute coronary syndrome within 6 months prior to Screening, significant or unstable cardiac disease, uncontrolled diabetes, bleeding diathesis or coagulopathy, or prior solid organ or bone marrow transplant

2. Concomitant clinically significant liver disease, including but not limited to viral hepatitis caused by other pathogens, hemochromatosis, Wilson's disease, primary biliary cholangitis, autoimmune liver disease, alcoholic liver disease, drug-induced liver injury, or current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy, hepatorenal syndrome, or variceal hemorrhage).

3. Any severe infection (other than chronic HBV infection) within 1 month prior to randomization and/or requiring intravenous anti-infective therapy.

4. History of immune thrombocytopenia.

5. Current suspected liver cirrhosis and/or evidence of cirrhosis defined as liver stiffness measurement (LSM) >9 kPa by FibroScan® or equivalent imaging modality (e.g., ultrasound elastography).

6. History of liver cirrhosis defined by liver biopsy or by LSM >12 kPa by FibroScan® or equivalent imaging modality.

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, including but not limited to nephrotic syndrome, any form of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, or uncontrolled hypertension.

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. Abnormal laboratory values at Screening meeting any of the following criteria:

    1. Serum albumin <3.5 g/dL
    2. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² calculated using the CKD-EPI equation (or JSN-CKDI equation for participants in Japan)
    3. International normalized ratio (INR) >1.25
    4. Platelet count <125 × 10⁹/L
    5. Total bilirubin >1.5 × upper limit of normal (ULN). Participants with benign unconjugated hyperbilirubinemia (Gilbert's syndrome) may be enrolled if deemed eligible by the Investigator
    6. Urine albumin-to-creatinine ratio (uACR) >0.3 mg/mg (300 mg/g) on two consecutive measurements following a positive or weakly positive urine protein result on routine urinalysis
    7. Borderline positive or positive antineutrophil cytoplasmic antibody (ANCA) results requiring further evaluation (MPO-ANCA and PR3-ANCA). Eligibility requires review of complete medical history and confirmation of no past or current vasculitic, inflammatory, or autoimmune disease by the Sponsor or Sponsor-designated Medical Monitor

11. History of vasculitis or presence of signs or symptoms suggestive of vasculitis (e.g., vasculitic rash, skin ulceration, unexplained recurrent hematuria), or history or presence of diseases associated with vasculitis (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).

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 that, in the Investigator's judgment, may interfere with study participation or 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, unless the Investigator determines the medication can be safely discontinued prior to first IP administration. Participants taking low-dose aspirin must agree to discontinue use during the study if protocol-specified conditions are met.

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