Study of AHB-171 in Chronic Hepatitis B Participants

• AHB-171 (Drug): Injection
• Placebo matching [Investigational Product] (Drug): Injection
• Nucleos(t)ide Analogue (NA) (Drug): Oral administration

Primary outcomes

• Incidence of Adverse Events (AEs) [Safety and Tolerability] [Up to 72 weeks]
• The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: the maximum observed plasma concentration (Cmax) of AHB-171. [Up to 72 weeks]
• The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: the area under the concentration-time curve extrapolated to infinity (AUCinf ) of AHB-171 [Up to 72 weeks]
• Incidence of clinically significant changes in Vital Signs [Safety and Tolerability] [Up to 72 weeks]: Vital signs include body temperature, pulse rate, respiratory rate, and blood pressure
• Incidence of clinically significant changes in cardiac parameters [Safety and Tolerability] [Up to 72 weeks]: 12-lead electrocardiogram (ECG) abnormalities will be reported, with parameters evaluated including PR interval, QRS duration, QT/QTc interval.
• Incidence of laboratory abnormalities [Safety and Tolerability] [Up to 72 weeks]
• The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: area under the curve from the time of dosing to the last measurable concentration (AUClast) of AHB-171 [Up to 72 weeks]

Secondary outcomes

• Absolute serum HBsAg (Hepatitis B surface antigen) and change from baseline across all evaluated timepoints in the study [Up to 72 weeks]
• Absolute serum HBV (Hepatitis B virus) DNA and change from baseline across all evaluated timepoints in the study. [Up to 72 weeks]
• Absolute serum HBeAb (Hepatitis B e Antibody) and change from baseline across all evaluated timepoints in the study. [Up to 72 weeks]
• Proportion of participants achieving pre-specified HBsAg reduction levels or absolute thresholds across all evaluated timepoints in the study. [Up to 72 weeks]
• Proportion of participants achieving HBsAg < or ≥ LOD (limit of detection) and/or HBV DNA < or ≥ LLOQ (lower limit of quantitation) across all evaluated timepoints in the study. [Up to 72 weeks]
• Proportion of participants achieving pre-specified HBV DNA levels or absolute thresholds across all evaluated timepoints in the study. [Up to 72 weeks]
• Time to achieving pre-specified HBsAg levels or absolute thresholds across all evaluated timepoints in the study [Up to 72 weeks]
• Change from baseline in alanine aminotransferase (ALT) levels [Up to 72 weeks]
• Proportion of participants with ALT normalization among those with elevated ALT at baseline across all evaluated timepoints in the study. [Up to 72 weeks]
• Proportion of participants achieving anti-HBs seroconversion across all evaluated timepoints in the study. [Up to 72 weeks]
• Proportion of participants experiencing virologic relapse. [Up to 72 weeks]: Virologic relapse is defined as HBV DNA meeting a protocol-specified threshold value at 2 consecutive visits
• Time to participants experiencing virologic relapse. [Up to 72 weeks]: Virologic relapse is defined as HBV DNA meeting a protocol-specified threshold value at 2 consecutive visits
• Proportion of participants with treatment emergent AEs (TEAEs), serious AEs (SAEs), or discontinuation due to AEs. [Up to 72 weeks]
• Proportion of participants with anti-drug antibodies (ADA) to AHB-171. [Up to 72 weeks]
• ADA titers in participants with ADA to AHB-171 across all evaluated timepoints in the study. [Up to 72 weeks]
• Plasma PK parameters AUC of AHB-171 and metabolites. [Up to 72 weeks]
• Plasma PK parameter Cmax of AHB-171 and metabolites. [Up to 72 weeks]
• Plasma PK parameter Time to Peak Concentration (tmax) of AHB-171 and metabolites. [Up to 72 weeks]
• Plasma PK parameter apparent clearance (CL [clearance]/F [Bioavailability]) of AHB-171 and metabolites. [Up to 72 weeks]
• Urine PK parameter cumulative amount excreted (Ae) of AHB-171 and metabolites. [Up to 72 weeks]
• Urine PK parameter renal clearance (CLr) of AHB-171 and metabolites. [Up to 72 weeks]
• Absolute serum HBV ribonucleic acid (RNA) and change from baseline across all evaluated timepoints in the study. [Up to 72 weeks]
• Absolute serum HBcrAg (Hepatitis B core-related antigen) and change from baseline across all evaluated timepoints in the study [Up to 72 weeks]
• Absolute serum HBeAg (Hepatitis B e antigen) and change from baseline across all evaluated timepoints in the study. [Up to 72 weeks]
• Proportion of participants with hs-HBsAg (high-sensitivity HBsAg) <LLOQ across all evaluated timepoints in the study. [Up to 72 weeks]
• Absolute serum HBsAb (Hepatitis B surface Antibody) and change from baseline across all evaluated timepoints in the study. [Time Frame: Up to 72 weeks]
• Time to first hs-HBsAg <LLOQ, assessed at scheduled visits [Up to 72 weeks]

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Male or female participants, aged 18-65 years old (inclusive)
* Body Mass Index between 19 to 35 kg/m2 (inclusive)
* Body weight > or = 45 kg.
* Documented HBV infection for ≥6 months prior to randomization.
* For Parts A and B, on stable approved NA monotherapy for at least 6 months prior to randomization.
* For Part C and D only, not on any NA monotherapy for at least 6 months prior to randomization.
* Screening electrocardiogram (ECG) without clinically significant abnormalities
* Females of childbearing potential must not be breastfeeding, must have a negative serum pregnancy test at Screening, and a negative urine/serum pregnancy test before dosing (unless permanently sterile or >2 years postmenopausal).
* Males and females of childbearing potential must agree to use protocol specified reliable contraception throughout the study.
* Screening HBV DNA, HBsAg and ALT must meet prespecified requirements.

Exclusion Criteria:

* Significant medical conditions other than chronic HBV (e.g. recent heart issues, unstable cardiac disease, uncontrolled diabetes, bleeding disorders, prior organ transplant).
* Other clinically significant liver diseases (e.g. hepatitis from other causes, autoimmune or alcoholic liver disease, prior liver failure).
* History of suspected or confirmed cirrhosis (based on FibroScan® or biopsy).
* Current, past, or suspected liver cancer, or elevated alpha-fetoprotein (AFP) ≥ 20 ng/mL.
* HBV-related extrahepatic diseases (e.g. kidney or vascular conditions).
* Severe infection (other than chronic HBV infection) within 1 month before randomization requiring intravenous treatment.
* Active infections: human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV) or syphilis (exceptions if RNA negative).
* Abnormal lab results (e.g. low albumin, reduced kidney function, abnormal INR, low platelets, high bilirubin, abnormal blood counts, significant proteinuria).
* History or signs of vasculitis or related autoimmune diseases.
* Malignancy within 5 years (except non-melanoma skin cancer).
* Allergy to study drug components.
* Recent major surgery/trauma (within 3 months) or planned surgery during study.
* Alcohol or substance abuse affecting compliance.
* Pregnancy, breastfeeding, or unwillingness to follow reproductive restrictions.
* Participation in another clinical trial or recent investigational product use.
* Prior treatment with any antisense oligonucleotide or small interfering RNA therapies.
* Recent or ongoing use of immunosuppressive/biologic therapies, certain vaccines, bulevirtide, or unapproved herbal remedies.
* Need for long-term anticoagulants/antiplatelet drugs (unless safely stopped).
* Any other condition making the participant unsuitable (per investigator).