A Study on the Safety, Efficacy and Immune Response Following Sequential Treatment With an Anti-sense Oligonucleotide Against Chronic Hepatitis B (CHB) and Chronic Hepatitis B Targeted Immunotherapy (CHB-TI) in CHB Patients Receiving Nucleos(t)Ide Analogue (NA) Therapy

NCT05276297 | Completed Phase 2 DMC

• 3 other identifiers: 2170232021-003567-102024-512352-38-00
• Study Type: interventional
• Target: 174
• Locations: 15 countries
• Sites: 51

Brief Summary

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.

Conditions

Hepatitis B, Chronic

Keywords

Hepatitis B virus; Chronic Hepatitis B; Chronic Hepatitis B targeted immunotherapy; Bepirovirsen; Safety; Reactogenicity; Efficacy; Immunogenicity

Outcome Measures

Primary Outcomes (4)

• Percentage of participants reporting any grade 3 adverse event (AE) from first dose of GSK3228836 up to study end

  An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. A grade 3 AE is an AE which prevents normal, everyday activities (in adults, such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy).

  From first dose of GSK3228836 (Treatment 1 -Day 1) up to study end (Treatment 2-Day 505/Day 673/Day 841)

• Percentage of participants reporting any serious adverse event (SAE) from first dose of GSK3228836 up to study end

  An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or is an abnormal pregnancy outcome.

  From first dose of GSK3228836 (Treatment 1-Day 1) up to study end (Treatment 2-Day 505/Day 673/Day 841)

• 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. AESI related to GSK3528869A include liver disease-related (LDR) AEs, hematological AESI or potential immune-mediated diseases (pIMDs). A grade 3 AE is an AE which prevents normal, everyday activities (in adults, such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy).

  From first dose of GSK3228836 (Treatment 1-Day 1) up to study end (Treatment 2-Day 505/Day 673/Day 841)

• 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. Rescue medication is defined as any medication initiated for the purpose of antiviral suppression other than the background stable NA therapy irrespective of the reason.

  For up to 24 weeks after the planned end of active treatment (planned end of active treatment = Treatment 1-Day 78 for ASO12 group, Treatment 1-Day 162 for ASO24 group and Treatment 2-Day 169 for ASO12-TI and ASO24-TI groups)

Secondary Outcomes (28)

• Percentage of participants reporting each solicited administration site event post-GSK3528869A study intervention administration

  Within 7 days post-administration (day of administration + 6 subsequent days) of each dose of GSK3528869A study intervention

• Percentage of participants reporting each solicited systemic event post-GSK3528869A study intervention administration

  Within 7 days post-administration (day of administration + 6 subsequent days) of each dose of GSK3528869A study intervention

• Percentage of participants reporting any unsolicited AE post-GSK3528869A study intervention administration

  Within 30 days post-administration (day of administration + 29 subsequent days) of each dose of GSK3528869A study intervention

• Percentage of participants reporting any AE from first dose of GSK3228836 up to study end

  From first dose of GSK3228836 (Treatment 1-Day 1) up to study end (Treatment 2-Day 505/Day 673/Day 841)

• Percentage of participants reporting any AESIs from first dose of GSK3228836 up to study end

  From first dose of GSK3228836 (Treatment 1-Day 1) up to the study end (Treatment 2-Day 505/Day 673/Day 841)

Study Arms (4)

ASO24-TI Group

EXPERIMENTAL

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. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks.

Drug: GSK3228836; Biological: GSK3528869A

ASO24 Group

ACTIVE COMPARATOR

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. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks.

Drug: GSK3228836; Drug: Control

ASO12-TI Group

EXPERIMENTAL

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. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks.

Drug: GSK3228836; Biological: GSK3528869A

ASO12 Group

ACTIVE COMPARATOR

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. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks.

Drug: GSK3228836; Drug: Control

Interventions

GSK3528869A BIOLOGICAL

The GSK3528869A chronic Hepatitis B targeted immunotherapy (CHB-TI) consisting of 4 doses administered intramuscularly as follows: * 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.

ASO12-TI Group; ASO24-TI Group

Control DRUG

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.

ASO12 Group; ASO24 Group

GSK3228836 DRUG

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.

Also known as: Bepirovirsen

ASO12 Group; ASO12-TI Group; ASO24 Group; ASO24-TI Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
• A male or female between, and including, 18 and 65 years of age at the time of signing of the informed consent (except for South Korea, where a male or female between, and including, 19 and 65 years of age at the time of signing of the informed consent can participate in the study).
• Participants who are Hepatitis B envelop antigen (HBeAg) positive or negative.
• 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.
• CHB patient, under and adherent to treatment with a NA with high barrier to resistance (e.g. entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide).
• 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.
• A male participant is eligible if he agrees to the following during the intervention period and for at least 90 days after the last dose of study intervention:
• Refrain from donating sperm
• AND be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below.
• Agree to use a male condom \[and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak\] when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
• A female participant is eligible:
• If she is not pregnant or breastfeeding

You may not qualify if:

• Medical conditions
• Clinically significant abnormalities, aside from chronic HBV infection.
• Co-infection with:
• Current or past history of HCV
• HIV
• HDV
• History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by:
• 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.
• Diagnosed or suspected HCC.
• History of:
• malignancy within the past 5 years except of specific cancers that are cured by surgical resection
• vasculitis or presence of symptoms and signs of potential vasculitis
• extrahepatic disorders possibly related to HBV immune conditions

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (51)

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Sliven, 8800, Bulgaria

Location

GSK Investigational Site

Sofia, 1407, Bulgaria

Location

GSK Investigational Site

Sofia, 1431, Bulgaria

Location

GSK Investigational Site

Sofia, 1784, Bulgaria

Location

GSK Investigational Site

Sofia, 1797, Bulgaria

Location

GSK Investigational Site

Veliko Tarnovo, 5000, Bulgaria

Location

GSK Investigational Site

Vratsa, 3000, Bulgaria

Location

GSK Investigational Site

Clichy, 92118, France

Location

GSK Investigational Site

Créteil, 94010, France

Location

GSK Investigational Site

Lyon, 69317, France

Location

GSK Investigational Site

Strasbourg, 67091, France

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Frankfurt, 60590, Germany

Location

GSK Investigational Site

Leipzig, 04103, Germany

Location

GSK Investigational Site

Pokfulam, Hong Kong

Location

GSK Investigational Site

Bergamo, Italy

Location

GSK Investigational Site

Milan, 20122, Italy

Location

GSK Investigational Site

Milan, 20157, Italy

Location

GSK Investigational Site

Roma, 00133, Italy

Location

GSK Investigational Site

Rozzano MI, 20089, Italy

Location

GSK Investigational Site

Makati City, 1229, Philippines

Location

GSK Investigational Site

Pasig, 1605, Philippines

Location

GSK Investigational Site

Krakow, 31-202, Poland

Location

GSK Investigational Site

Mysłowice, 41-400, Poland

Location

GSK Investigational Site

Łańcut, 37-100, Poland

Location

GSK Investigational Site

Cluj-Napoca, 400162, Romania

Location

GSK Investigational Site

Craiova Dolj, 200515, Romania

Location

GSK Investigational Site

Singapore, 119074, Singapore

Location

GSK Investigational Site

Singapore, 169608, Singapore

Location

GSK Investigational Site

Barcelona, 08011, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Madrid, 28222, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Vigo, 36071, Spain

Location

GSK Investigational Site

Chiayi City, 600, Taiwan

Location

GSK Investigational Site

Kaohsiung City, 807, Taiwan

Location

GSK Investigational Site

Linkou - Taoyuan Hsien, 333, Taiwan

Location

GSK Investigational Site

Taichung, 404, Taiwan

Location

GSK Investigational Site

Taichung, 40705, Taiwan

Location

GSK Investigational Site

Tainan, 704, Taiwan

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

GSK Investigational Site

Istanbul, 6690, Turkey (Türkiye)

Location

GSK Investigational Site

Rize, 53200, Turkey (Türkiye)

Location

GSK Investigational Site

Cottingham, HU16 5JQ, United Kingdom

Location

GSK Investigational Site

Leicester, LE1 5WW, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Open-label for Treatment 1 and single-blinded for Treatment 2.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 11, 2022
• Study Start: March 22, 2022
• Primary Completion: August 5, 2025
• Study Completion: August 5, 2025
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

TW (6); FR (4); RO (2); TU (2); BU (7); HK (1); GB (2); TH (2); DE (3); ES (9); PH (2); IT (5); SG (2); PL (3); BE (1)