--- title: "Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Study 217023 bepirovirsen followed by targeted immunotherapy" description: "Formulary evidence on Hibsago (bepirovirsen, GSK3228836) in Chronic hepatitis B virus infection in adults without cirrhosis: Study 217023 bepirovirsen followed by targeted immunotherapy. Covers Objective, Location and study date, Study design, Eligibility criteria, Treatment, Study outcomes, and 2 further headings. 18 evidence topics quoted from 3 sources." canonical: "https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/clinical-evidence/study-217023-bepirovirsen-followed-by-targeted-immunotherapy" published: "2026-10-21T22:39:04-04:00" modified: "2026-10-22T19:07:03-04:00" --- # Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Study 217023 bepirovirsen followed by targeted immunotherapy ## 3.1.10 Study 217023 Bepirovirsen Followed by Targeted Immunotherapy ### 3.1.10.1 Objective #### Aim stated in the registry record > “This study will assess the safety, efficacy and immune response following the sequential treatment of GlaxoSmithKline's (GSK) ASO compound (GSK3228836) and CHB-TI (GSK3528869A) in participants 18 to 65 years stable on NA treatment for CHB. The aim is to quantify the efficacy of sequential therapy as well as to determine an added value of sequential therapy over GSK3228836 therapy in CHB patients treated with NAs. In addition, the study will assess the effect of different treatment durations of GSK3228836 (12 or 24 weeks) prior to initiating GSK3528869A treatment.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Basis for combining HBsAg reduction with therapeutic immunization > “Therapeutic vaccines likely require combination therapy for success.” > “For example, pretreatment with agents that reduce HBsAg before therapeutic immunization and/or concurrent treatment with checkpoint inhibitors or other immune-activating agents might improve efficacy.” Source: [Jeng et al. (2026)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13496306/) ### 3.1.10.2 Location and Study Date #### Study dates and status in the registry record | Field | Registry entry | | --- | --- | | Recruitment status | “Completed” | | Study start (actual) | “2022-03-22” | | Primary completion (actual) | “2025-08-05” | | Study completion (actual) | “2025-08-05” | | First posted | “2022-03-11” | | Last update posted | “2025-12-30” | Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Number of study locations > “This study has 51 locations” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) ### 3.1.10.3 Study Design #### Phase 2, single-blinded, randomized, controlled design > “A Phase 2, Single-blinded, Randomised, Controlled Multi-country Study to Evaluate the Safety, Reactogenicity, Efficacy and Immune Response Following Sequential Treatment With an Anti-sense Oligonucleotide (ASO) Against Chronic Hepatitis B (CHB) Followed by Chronic Hepatitis B Targeted Immunotherapy (CHB-TI) in CHB Patients Receiving Nucleos(t)Ide Analogue (NA) Therapy” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Design details in the registry record | Field | Registry entry | | --- | --- | | Allocation | “Randomized” | | Interventional model | “Sequential Assignment” | | Masking description | “Open-label for Treatment 1 and single-blinded for Treatment 2.” | | Phase | “Phase 2” | | Other study identifiers | “217023” | | EudraCT number | “2021-003567-10” | | EU trial number | “2024-512352-38-00” | Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Follow-up period shortened during the study > “The study follow-up period was reduced from 2 years post last dose to at least 1 year post last dose, with Visit Treatment 2-Day 505 defined as the last visit of the study.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) ### 3.1.10.4 Eligibility Criteria #### Key inclusion criteria > “Participants who have documented chronic HBV infection >=6 months prior to screening and currently stable on NA therapy defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study.” > “Participants with ALT <=2x upper limit of normal (ULN) (i.e., no ALT >2x ULN) documented in approximately the last 6 months.” > “Participants with plasma or serum HBsAg concentration >100 IU/mL.” > “Participants must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Key exclusion criteria: cirrhosis definitions and laboratory thresholds > “both AST-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7” > “Liver biopsy (METAVIR Score F4) or Liver stiffness >12 kPa” > “FibroScan TE score >9.6 kPa and FibroTest score >0.59 at Screening.” > “GFR <60 mL/min/1.73m^2” > “PLT count <140x10^9/L” > “Positive (or borderline positive) ANCA at screening.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) ### 3.1.10.5 Treatment #### Bepirovirsen (GSK3228836) dosing in treatment 1 > “2 doses of GSK3228836 study intervention administered subcutaneously once per week for 12 weeks (Day 1 up to Day 78) to participants in ASO12-TI and ASO12 groups, or for 24 weeks (Day 1 up to Day 162) to participants in ASO24-TI and ASO24 groups, plus loading doses administered at Day 4 and Day 11 (2 doses each day) to participants in all groups during Treatment 1 period.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Targeted immunotherapy (GSK3528869A) or control in treatment 2 > “1 dose of the Chimpanzee adenovectored HBV vaccine (ChAd155-hIi-HBV) at Day 1 of Treatment 2 period.” > “1 dose of the Modified Vaccinia Virus Ankara HBV vaccine (MVA-HBV) at Day 57 of Treatment 2 period.” > “2 subsequent doses of the AS01B-4-adjuvanted HBc-HBs proteins (HBc-HBs/AS01B-4) administered at Day 113 and Day 169 of Treatment 2 period.” > “4 doses of non-active control administered intramuscularly in the deltoid region of the non-dominant arm at Days 1, 57, 113 and 169 to participants in ASO24 and ASO12 control groups during Treatment 2 period.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### Four treatment groups | Group | Registry entry | | --- | --- | | ASO24-TI | “Eligible participants receive GSK3228836 (Treatment 1) study intervention for 24 weeks of Treatment 1 period, followed by GSK3528869A (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period.” | | ASO24 | “Eligible participants receive GSK3228836 (Treatment 1) study intervention for 24 weeks of Treatment 1 period, followed by non-active control (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period.” | | ASO12-TI | “Eligible participants receive GSK3228836 (Treatment 1) study intervention for 12 weeks of Treatment 1 period, followed by GSK3528869A (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period.” | | ASO12 | “Eligible participants receive GSK3228836 (Treatment 1) study intervention for 12 weeks of Treatment 1 period, followed by non-active control (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period.” | Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) ### 3.1.10.6 Study Outcomes #### 3.1.10.6.1 Rationale for Using Grade 3 Adverse Events, Serious Adverse Events, and Sustained Virologic Response as the Primary Endpoints ##### Registered primary safety outcomes > “Percentage of participants reporting any grade 3 adverse event (AE) from first dose of GSK3228836 up to study end” > “Percentage of participants reporting any serious adverse event (SAE) from first dose of GSK3228836 up to study end” > “Percentage of participants reporting any adverse events of special interest (AESIs) grade 3 or higher from first dose of GSK3228836 up to study end” > “AESI related to GSK3228836 treatment include thrombocytopenia, alanine transaminase (ALT) increases, vascular inflammation and complement activation, renal injury or injection site reactions.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) ##### Registered primary efficacy outcome: sustained virologic response > “Percentage of participants who achieve sustained virologic response (SVR) for 24 weeks after the planned end of active treatment in the absence of rescue medication, and difference between treatment arms (corresponding to GSK3228836 regimens)” > “SVR is defined as Hepatitis B surface antigen (HBsAg) below (<) lower limit of quantification (LLOQ) and HBV deoxyribose nucleic acid (DNA) < LLOQ.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) ##### Reactogenicity of the immunotherapy regimen given alone in an earlier trial > “Grade 3 solicited adverse events (AEs) (median duration: 2–3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1).” Source: [Jeng et al. (2026)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13496306/) ### 3.1.10.7 Statistical Analysis Description #### 3.1.10.7.1 Number of Participants (Planned and Analyzed) ##### Enrollment in the registry record | Field | Registry entry | | --- | --- | | Enrollment (actual) | “174” | Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297) #### 3.1.10.7.2 Description of Analysis Sets No evidence found. ### 3.1.10.8 Results #### 3.1.10.8.1 Participant Disposition No evidence found. #### 3.1.10.8.2 Baseline Characteristics No evidence found. #### 3.1.10.8.3 Efficacy Results No evidence found. #### 3.1.10.8.4 Health-related Quality of Life and Patient-reported Outcomes No evidence found. #### 3.1.10.8.5 Safety Results No evidence found. ### 3.1.10.9 Study Limitations #### Summary: study limitations Study 217023 enrolled 174 participants and was completed in August 2025; the sponsor submitted results to ClinicalTrials.gov on 2026-08-04, but no results are posted and no publication was identified, so its safety and efficacy outcomes cannot be assessed. The bepirovirsen regimens in this study (12 or 24 weeks with loading doses on days 4 and 11) were followed by an investigational immunotherapy or a non-active control, and only the 24-week regimen corresponds to the approved treatment duration. The follow-up period was reduced from 2 years to at least 1 year after the last dose during the study, and the immunotherapy regimen given alone produced no HBsAg loss in an earlier trial. Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297); [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297?tab=results); [Jeng et al. (2026)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13496306/) #### Results submitted but not posted > “No Study Results Posted on ClinicalTrials.gov” > “The sponsor or the investigator has submitted results.” Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297?tab=results) | Field | Registry entry | | --- | --- | | Results submitted to ClinicalTrials.gov | “2026-08-04” | Source: [ClinicalTrials.gov NCT05276297](https://clinicaltrials.gov/study/NCT05276297?tab=results) ## Related pages - [Hibsago (bepirovirsen): Chronic hepatitis B virus infection in adults without cirrhosis](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Terms and abbreviations](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/terms-and-abbreviations) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/terms-and-abbreviations.md) - [Hibsago (bepirovirsen): Chronic hepatitis B virus infection in adults without cirrhosis](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/executive-summary) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/executive-summary.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Product information and disease description](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Clinical evidence](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/clinical-evidence) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/clinical-evidence.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Economic information and modeling report](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/economics) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/economics.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: References](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/references) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/references.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: new drug review](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/monograph/review) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/monograph/review.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: cost-effectiveness analyses and utility weights](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/cost-effectiveness-analyses) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/cost-effectiveness-analyses.md)