A Study to Evaluate the Efficacy and Safety of Bepirovirsen in Participants Receiving Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B Virus InfectionB -Definite

For female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

• Is a woman of non-childbearing potential (WONCBP) OR
• Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1 percent (%) per year) and preferably with low user dependency, for a period of 28 days prior to and during the Bepirovirsen Treatment Stage, and for at least 7 days after the last dose of bepirovirsen; and agrees not to donate eggs/ova/oocytes for the purpose of reproduction during the Bepirovirsen Treatment Stage. The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated) in relationship to the first dose of bepirovirsen.

A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of bepirovirsen.

• If a urine pregnancy test cannot be confirmed as negative (it has an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

History of, or suspected, liver cirrhosis and/or evidence of cirrhosis, defined as: a. Both Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) greater than (>) 2 and FibroSure/FibroTest score > 0.7 at the Screening visit. b. In addition, regardless of the APRI or FibroSure/FibroTest score at the Screening visit, the participant must be excluded from this study if any prior medical record before the Screening visit shows at least one of the following:

• Liver biopsy with a METAVIR score of F4.
• Liver stiffness measurement of greater than or equal to (>=)12 kilopascal (kPa) by ultrasound elastography or (>=) 5 kPa by magnetic resonance elastography.

Current or past extrahepatic disorders (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension) that are considered possibly related to HBV, in the opinion of the Investigator. Current or past alcohol or drug abuse/dependence: a. Current alcohol use that would interfere with participant compliance, in the opinion of the Investigator. b. Current or past drug abuse/dependence that would interfere with participant compliance, in the opinion of the Investigator.

• This refers to illicit drug abuse or misuse of medications and substances with abuse potential. Medications used as directed, whether over the counter or prescribed, are acceptable and do not meet this exclusion criterion.

Laboratory results as follows:

• Serum albumin <= 3.5 grams per deciliter (g/dL)
• International normalized ratio (INR) >1.25
• Platelet count <100 x 10^9/L
• Total bilirubin >1.25 x ULN – Participants with Gilbert's syndrome can be included if direct bilirubin <= 1.25x ULN. – The Investigator needs to document this medical condition in the eCRF.
• Urine albumin to creatinine ratio (uACR) >0.3 milligrams per milligram (mg/mg) (>300 mg/gram [g]). In the event of an uACR above this threshold, eligibility may be determined by a repeat measurement. – If one or both components of the urine albumin to creatinine ratio are outside the reportable range, an accurate ratio cannot be reported. In such cases, the Investigator should review both components and interpret them in conjunction with other clinical characteristics (e.g., history of diabetes, hypertension).