A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

The study is intended to evaluate the efficacy and safety of 2 different doses of DAP/TOM followed by bepirovirsen in participants living with CHB on standard of care nucleos(t)ide analogue (NA) therapy. The study also aims to identify an optimal dose of DAP/TOM for sequenced therapy with bepirovirsen for further clinical development and to assess the contribution of DAP/TOM to the sequential regimen.


Eligibility Criteria:
Inclusion Criteria:

* Age: At least 18 years of age at the time of signing the informed consent.
* Documented chronic HBV infection \>=6 months prior to Screening AND currently receiving stable NA therapy defined as receiving an NA regimen form at least 6 months prior to Screening and with no planned changes to their stable regimen over the duration of the study.
* Plasma or serum HBsAg concentration \>100 international units per milliliter (IU/mL)
* Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA \<90 IU/mL.
* Alanine aminotransferase \<=2\* upper limit of normal (ULN)
* Participants who are willing and able to cease their NA treatment in accordance with the protocol.
* Male and Female

Exclusion Criteria:

* Clinically significant abnormalities, aside from chronic HBV infection in medical history (e.g., moderate-severe liver disease other than chronic HBV, acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis coagulopathy) or clinically significant physical examination findings.
* Coinfection with Hepatitis C (cured \<12 months at the time of screening), Human immunodeficiency virus or hepatitis D virus.
* History of or suspected liver cirrhosis and/or evidence of cirrhosis.
* Diagnosed or suspected hepatocellular carcinoma.
* History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (example, skin cancer). Participants under evaluation for possible malignancy are not eligible.
* History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause), current or history of an autoimmune condition or history/presence of other diseases that may be associated with vasculitis condition (example, systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
* History of extrahepatic disorders possibly related to HBV immune conditions (example, nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
* History of alcohol or drug abuse/dependence:
* Currently taking, or took within 3 months of screening, any immunosuppressing drugs (example, prednisone), other than a short course of therapy (\<=2 weeks) or topical/inhaled steroid use.
* Participants, to whom immunosuppressive treatment (including therapeutic doses of steroids) is contraindicated, should not be considered for enrollment in the study.
* Currently taking, or has taken within 6 months of Screening, any interferon-containing therapy.
* Participants requiring anti-coagulation therapies (example, warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of Investigational medicinal product (IMP) treatment, by the discretion of the investigator. Occasional use is permitted.
* Prior hepatitis B treatment with bepirovirsen, DAP/TOM, or another oligonucleotide or small interfering ribonucleic acid (RNA) (siRNA).
* Prior non-hepatitis B treatment with an oligonucleotide or siRNA within 12 months prior to the first dosing day.
* Fridericia's QT correction formula (QTcF) \>=450 millisecond (msec) (if single electrocardiogram \[ECG\] at screening shows QTcF \>=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).
* History of/sensitivity to bepirovirsen, DAP/TOM or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
* Participants who do not wish to discontinue taking NA therapy for their chronic HBV infection.