Study of VIR-2218, VIR-3434, and/or PEG-IFNα in Subjects With Chronic Hepatitis B Virus Infection

• VIR-2218 (Drug), also known as Elebsiran: VIR-2218 given by subcutaneous injection
• VIR-3434 (Drug), also known as Tobevibart: VIR-3434 given by subcutaneous injection
• PEG-IFNα (Drug): PEG-IFNα given by subcutaneous injection

Primary outcomes

• Proportion of participants with treatment-emergent adverse events (TEAEs) [Up to 72 weeks]
• Proportion of participants with serious adverse events (SAEs) [Up to 72 weeks]
• Proportion of participants with hepatitis B surface antigen (HBsAg) loss (defined as undetectable HBsAg) at end of treatment [Up to 48 weeks]
• Proportion of participants with HBsAg loss (defined as undetectable HBsAg) at 24 weeks post-end of treatment [Up to 72 weeks]

Secondary outcomes

• Absolute serum HBsAg and change from baseline across all timepoints in the study [Up to 110 weeks]
• Nadir and maximum reduction of serum HBsAg from baseline [Up to 110 weeks]
• Proportion of participants achieving sustained suppression of HBV DNA (< lower limit of quantification (LLOQ) for >= 24 weeks after discontinuation of all treatment, including NRTIs) [Up to 110 weeks]
• For hepatitis B e-antigen (HBeAg)-positive participants: Proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion at any timepoint [Up to 110 weeks]
• For HBeAg-positive participants: Time to HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion [Up to 110 weeks]
• Cmax [Up to 110 weeks]
• AUClast [Up to 110 weeks]
• t1/2 [Up to 110 weeks]
• CL/F [Up to 110 weeks]
• Number of participants with incidence and titers of anti-drug antibody (ADA) (if applicable) to VIR-3434 [Up to 110 weeks]
• Proportion of participants meeting criteria for nucleotide reverse transcriptase inhibitors (NRTI) discontinuation [Up to 60 weeks]
• Proportion of participants meeting criteria for NRTI retreatment [Up to 110 weeks]
• Proportion of participants achieving undetectable HBsAg and sustained suppression of HBV DNA [below the LLOQ, target not detected (TND)] >/= 24 weeks after discontinuation of all treatment, including NRTIs [Up to 110 weeks]
• Proportion of participants with serum HBsAg < 10 IU/mL at end of treatment [Up to 48 weeks]
• Proportion of participants with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment [Up to 72 weeks]: 48 weeks treatment + 24 weeks post-end of treatment
• Proportion of participants with anti-HBs seroconversion [Up to 110 weeks]
• Time to achieve nadir of serum HBsAg [Up to 110 weeks]
• Time to achieve serum HBsAg loss [Up to 110 weeks]

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Male or female ages 18 - <66 years
* Chronic HBV infection for >/= 6 months
* On NRTI therapy for >/= 2 months at the time of screening

Exclusion Criteria:

* Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation
* Significant fibrosis or cirrhosis
* History or evidence of drug or alcohol abuse
* History of chronic liver disease from any cause other than chronic HBV infection
* History of hepatic decompensation
* History of anaphylaxis
* History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434
* History of immune complex disease
* History of known contraindication to any interferon product

• Results publication: Noack J, Anglero-Rodriguez Y, Gall J, Zhou J, LeBlanc S, Liebow A, Bakardjiev A, Hebner CM, Purcell LA, Jadhav V, Corti D, Lempp FA. Combination therapy with tobevibart and elebsiran potently reduces hepatitis B virus surface antigen levels in preclinical in vivo models. Antimicrob Agents Chemother. 2026 Mar 4;70(3):e0112725. doi: 10.1128/aac.01127-25. Epub 2026 Jan 26. PMID 41586499