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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: GSK3228836; Biological: GSK3528869A; Drug: Control

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • GSK Investigational Site
• Bulgaria
  • Sliven, Bulgaria, 8800
    • GSK Investigational Site
  • Sofia, Bulgaria, 1431
    • GSK Investigational Site
  • Sofia, Bulgaria, 1407
    • GSK Investigational Site
  • Sofia, Bulgaria, 1784
    • GSK Investigational Site
  • Sofia, Bulgaria, 1797
    • GSK Investigational Site
  • Veliko Tarnovo, Bulgaria, 5000
    • GSK Investigational Site
  • Vratsa, Bulgaria, 3000
    • GSK Investigational Site
• France
  • Clichy Cedex, France, 92118
    • GSK Investigational Site
  • Créteil cedex, France, 94010
    • GSK Investigational Site
  • Lyon cedex 04, France, 69317
    • GSK Investigational Site
  • Strasbourg cedex, France, 67091
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • GSK Investigational Site
• Hong Kong
  • Pokfulam, Hong Kong
    • GSK Investigational Site
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00133
      • GSK Investigational Site
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20157
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20122
      • GSK Investigational Site
    • Rozzano (MI), Lombardia, Italy, 20089
      • GSK Investigational Site
• Philippines
  • Makati City, Philippines, 1229
    • GSK Investigational Site
  • Pasig, Philippines, 1605
    • GSK Investigational Site
• Poland
  • Krakow, Poland, 31-202
    • GSK Investigational Site
  • Lancut, Poland, 37-100
    • GSK Investigational Site
  • Myslowice, Poland, 41-400
    • GSK Investigational Site
• Romania
  • Cluj Napoca, Romania, 400162
    • GSK Investigational Site
  • Doij
    • Craiova, Doij, Romania, 200515
      • GSK Investigational Site
• Singapore
  • Singapore, Singapore, 119074
    • GSK Investigational Site
  • Singapore, Singapore, 169608
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08011
    • GSK Investigational Site
  • Madrid, Spain, 28006
    • GSK Investigational Site
  • Madrid, Spain, 28007
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Majadahonda (Madrid), Spain, 28222
    • GSK Investigational Site
  • Pontevedra, Spain, 36071
    • GSK Investigational Site
  • Santander, Spain, 39008
    • GSK Investigational Site
  • Sevilla, Spain, 41013
    • GSK Investigational Site
• Taiwan
  • Chiayi City, Taiwan, 600
    • GSK Investigational Site
  • Kaohsiung, Taiwan, 807
    • GSK Investigational Site
  • Taichung, Taiwan, 404
    • GSK Investigational Site
  • Taichung, Taiwan, 40705
    • GSK Investigational Site
  • Tainan, Taiwan, 704
    • GSK Investigational Site
  • Taoyuan, Taiwan, 333
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10330
    • GSK Investigational Site
  • Chiang Mai, Thailand, 50200
    • GSK Investigational Site
• Turkey
  • Ankara, Turkey, 6690
    • GSK Investigational Site
  • Rize, Turkey, 53200
    • GSK Investigational Site
• United Kingdom
  • Cottingham, Hull, United Kingdom, HU16 5JQ
    • GSK Investigational Site
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• 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
  • AND at least one of the following conditions applies:
  • Is not a WOCBP
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and for at least 90 days after the last dose of study treatment.
• 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 study intervention.

Exclusion criteria:

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
• Positive (or borderline positive) ANCA at screening.
• Low C3/C4 at screening AND evidence of past history or current manifestations of vasculitic/inflammatory/autoimmune conditions.
• History of alcohol or drug abuse/dependence.
• QTcF >=450 msec.

• Laboratory results as follows:

  • Serum albumin <3.5 g/dL
  • GFR <60 mL/min/1.73m^2
  • INR >1.25
  • PLT count <140x10^9/L
  • HGB <10 g/dl
  • T Bil >1.25xULN unless considered as clinically not significant by the Investigator
  • ACR >=0.03 mg/mg
• Medical history of hepatic decompensation.
• Planned or previous liver transplantation.
• Documented evidence of other currently active cause of hepatitis.
• Any other clinical condition that might pose additional risk to the participant due to participation in the study.
• Major congenital defects.
• Recurrent history or uncontrolled neurological disorders or seizures.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).

Prior/Concomitant therapy

• Use of any investigational or non-registered product other than the study interventions within 30 days before the first dose of study interventions, or their planned use during the study.
• Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which may have activity against HBV within 6 months prior the study.
• Currently taking, or took within 12 months of screening, any interferon-containing therapy.
• Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 months, except for adenovirus/adenovector-based COVID-19 vaccines that could be administered up to 30 days prior to the first study vaccine dose (applicable for all patients except for the patients in France) OR Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 months (applicable for the patients in France only).
• Planned administration/administration of a vaccine not foreseen by the study protocol within 14 days before the first dose and/or 30 days after the last dose of study intervention administration, with the exception of influenza vaccine that may be given at any time except within a 7-day period before or after each dose and COVID-19 vaccine that may be given at any time except within a 30-day period before or after each vaccine dose apart from COVID-19 mRNA based-vaccines that may be administered any time except for the period of 14 days before and 30 days after each study vaccine dose.

• Administration of:

  • long-acting immune-modifying drugs at any time during the study
  • immunoglobulins and/or any blood products or plasma derivatives within 3 months before the first dose of study interventions or planned administration during the study
• Chronic administration of immunosuppressants or other immune-modifying drugs within 3 months prior to the first study intervention (e.g. prednisone equivalent >=20 mg/day; >=10 mg/day applicable in Germany only). Inhaled and topical steroids are allowed.
• Participants for whom immunosuppressive treatment is not advised.
• Treatment with nephrotoxic drugs or competitors of renal excretion within 2 months prior to Screening or planned during the study.
• Participants requiring anti-coagulation therapies.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational/a non-investigational intervention.
• Previous participation in clinical trials with administration of either GSK3228836 or GSK3528869A.
• Previous participation in a clinical study in which he/she has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the study treatment or 90 days.
• Prior treatment with any other oligonucleotide/siRNA within 12 months prior to the first dosing day.

Other exclusions:

• Pregnant or lactating female.
• Female planning to become pregnant/to discontinue contraceptive precautions.
• Any study personnel or their immediate dependents, family, or household members.
• History of/sensitivity to GSK3228836, or components thereof, or a history of drug or other allergy that contraindicates their participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASO24-TI Group; 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; 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.; Other Names: Bepirovirsen; Biological: GSK3528869A; 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.
Active Comparator: ASO24 Group; 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; 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.; Other Names: Bepirovirsen; Drug: Control; 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.
Experimental: ASO12-TI Group; 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; 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.; Other Names: Bepirovirsen; Biological: GSK3528869A; 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.
Active Comparator: ASO12 Group; 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; 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.; Other Names: Bepirovirsen; Drug: Control; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 [T1]-Day 1) up to study end (Treatment 2 [T2]-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 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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants reporting each solicited administration site event post-GSK3528869A study intervention administration	The solicited administration site events include pain, redness and swelling.	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	The solicited systemic events include fatigue, fever, headache, myalgia, arthralgia and chills. Fever is defined as temperature equal to or above 38.0°C/100.4°F. The preferred location for measuring temperature is the oral cavity.	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	An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include both serious and non-serious AEs.	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	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.	From first dose of GSK3228836 (Treatment 1-Day 1) up to study end (Treatment 2-Day 841)
Percentage of participants reporting any AESIs from first dose of GSK3228836 up to study end	AESI related to GSK3228836 treatment include thrombocytopenia, ALT increases, vascular inflammation and complement activation, renal injury or injection site reactions. AESI related to GSK3528869A include liver disease-related AEs, hematological AESIs or pIMDs.	From first dose of GSK3228836 (Treatment 1-Day 1) up to the study end (Treatment 2-Day 841)
Percentage of participants reporting any pIMDs from first dose of GSK3528869A up to study end	pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.	From first dose of GSK3528869A (Treatment 2-Day 1) up to study end (Treatment 2-Day 841)
Percentage of participants reporting hematological, biochemical or urinalysis laboratory abnormalities at pre-defined time points during Treatment 1 period	Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.	At Days T1: 1 ,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 120, 127, 134, 141, 148, 155 and 162 (ASO24-TI & ASO24 groups) and at Days T1: 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78 (ASO12-TI & ASO12 groups)
Percentage of participants reporting hematological, biochemical or urinalysis laboratory abnormalities at pre-defined time points during Treatment 2 period	Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.	At Days T2: 1, 3, 8, 15, 31, 57, 64, 71, 87, 113, 120, 127, 143, 169, 176, 183 and 199
Percentage of participants reporting hematological, biochemical or urinalysis laboratory abnormalities at pre-defined time points during follow-up period	Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.	At Days T2: 225, 281, 337, 421, 505, 673 and 841
Percentage of participants who achieve quantitative Hepatitis B surface antigen assessment (qHBsAg) decrease and HBsAg loss at pre-defined time points from GSK3228836 baseline (Treatment 1-Day 1) up to end of treatment period	qHBsAg decrease is defined as ≥ 0.5 log decrease and ≥ 1-log decrease. The analysis is performed by considering the HBsAg status prior to GSK3228836 as baseline.	At Days T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162; T2:1,15,31,57,71,87,113,143,169,199 (ASO24-TI&ASO24 groups); T1:1,8,15,22,29,36,43,50,57,64,71,78; T2:1,15,31,57,71,87,113,143,169,199 (ASO12-TI&ASO12 groups)
Percentage of participants who achieve qHBsAg decrease and HBsAg loss at pre-defined time points from GSK3228836 baseline (Treatment 1-Day 1) up to end of Treatment 1 period	qHBsAg decrease is defined as ≥ 0.5 log decrease and ≥ 1-log decrease. The analysis is performed by considering the HBsAg status prior to GSK3228836 as baseline.	At Days T1: 1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162 (ASO24-TI & ASO24 groups) and at Days T1: 1,8,15,22,29,36,43,50,57,64,71,78 (ASO12-TI & ASO12 groups)
Percentage of participants who achieve qHBsAg decrease and HBsAg loss at pre-defined time points from GSK3528869A/control baseline (Treatment 2-Day 1) up to end of Treatment 2 period	qHBsAg decrease is defined as ≥ 0.5 log decrease and ≥ 1-log decrease. The analysis is performed by considering the HBsAg status prior to GSK3528869A/control as baseline.	At Days T2: 1, 15, 31, 57, 71, 87, 113, 143, 169 and 199
Changes in qHBsAg at pre-defined time points from GSK3228836 baseline (Treatment 1-Day 1) up to end of treatment period	Changes in serum qHBsAg from GSK3228836 baseline are expressed as geometric mean ratios (GMRs). The analysis is performed by considering the HBsAg status prior to GSK3228836 as baseline.	At Days T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162; T2:1,15,31,57,71,87,113,143,169,199 (ASO24-TI&ASO24 groups); T1:1,8,15,22,29,36,43,50,57,64,71,78; T2:1,15,31,57,71,87,113,143,169,199 (ASO12-TI&ASO12 groups)
Changes in qHBsAg at pre-defined time points from GSK3228836 baseline (Treatment 1-Day 1) up to end of Treatment 1 period	Changes in serum qHBsAg from GSK3228836 baseline are expressed as GMRs. The analysis is performed by considering the HBsAg status prior to GSK3228836 as baseline.	At Days T1: 1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162 (ASO24-TI & ASO24 groups) and at Days T1: 1,8,15,22,29,36,43,50,57,64,71,78 (ASO12-TI & ASO12 groups)
Changes in qHBsAg at pre-defined time points from GSK3528869A/control baseline (Treatment 2-Day 1) up to end of Treatment 2 period	Changes in serum qHBsAg from GSK3528869A/control are expressed as GMRs. The analysis is performed by considering the HBsAg status prior to GSK3528869A/control.	At Days T2: 1, 15, 31, 57, 71, 87, 113, 143, 169 and 199
Percentage of participants in ASO24-TI and ASO24 groups with HBsAg loss and anti-HBs seroconversion	A participant is counted only when both HBsAg loss and anti-HBs seroconversion are reported for the participant. Seroconversion is defined as the appearance of antibodies (i.e., concentrations/titer greater than or equal to the LLOQ) in the serum of participants seronegative before GSK3528869A administration.	At Days T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162 and at Days T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
Percentage of participants in ASO12-TI and ASO12 groups with HBsAg loss and anti-HBs seroconversion	A participant is counted only when both HBsAg loss and anti-HBs seroconversion are reported for the participant. Seroconversion is defined as the appearance of antibodies (i.e., concentrations/titer greater than or equal to the LLOQ) in the serum of participants seronegative before GSK3528869A administration.	At Days T1:1,8,15,22,29,36,43,50,57,64,71,78 and at Days T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
Geometric mean concentrations (GMCs) of qHBsAg for participants in ASO24-TI and ASO24 groups		At Days T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162 and at Days T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
Geometric mean concentrations (GMCs) of qHBsAg for participants in ASO12-TI and ASO12 groups		At Days T1:1,8,15,22,29,36,43,50,57,64,71,78 and at Days T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
Duration of SVR in terms of time to the first occurrence of HBsAg reversion and/or HBV DNA reversion	HBsAg reversion is defined as HBsAg >LLOQ or HBV DNA >LLOQ, confirmed by 2 consecutive visits at least 1 month apart.	From Treatment 1-Day 1 up to first occurrence of HBsAg reversion and/or HBV DNA reversion, assessed from Treatment 1-Day 1 up to Treatment 2-Day 841
Percentage of participants in ASO24-TI and ASO24 groups who experienced HBV DNA virologic breakthrough	HBV DNA virologic breakthrough is defined at 1-log increase from nadir in HBV DNA or HBV DNA becoming quantifiable after being below the LLOQ.	At Days T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,141,148,155,162 and at Days T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
Percentage of participants in ASO12-TI and ASO12 groups who experienced HBV DNA virologic breakthrough	HBV DNA virologic breakthrough is defined at 1-log increase from nadir in HBV DNA or HBV DNA becoming quantifiable after being below the LLOQ.	At Days T1:1,8,15,22,29,36,43,50,57,64,71,78 and at Days T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
Percentage of participants with anti-HBc antibody response		At Days T1: 1,29,57,85,113,141,162 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and T2:1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Anti-HBc antibody concentrations	Anti-HBc antibody concentrations are expressed as geometric mean concentrations (GMCs).	At Days T1: 1,29,57,85,113,141,162 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and T2:1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Percentage of participants who achieved HBsAg seroconversion	Seroconversion is defined as the appearance of antibodies (i.e., concentrations/titer greater than or equal to the LLOQ) in the serum of participants seronegative before GSK3528869A administration.	At Days T1: 1,29,57,85,113,141,162 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Percentage of participants with anti-HBs antibody response		At Days T1: 1,29,57,85,113,141,162 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Anti-HBs antibody concentrations	Anti-HBs antibody concentrations are expressed as GMCs.	At Days T1: 1,29,57,85,113,141,162 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Percentage of participants with anti-HBs antibody concentrations equal to or above (≥) 10 mIU/mL		At Days T1: 1,29,57,85,113,141,162 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Percentage of participants with anti-HBs antibody concentrations equal to or above (≥) 100 mIU/mL		At Days T1: 1,29,57,85,113,141,162 and at Days T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups) and at Days T1: 1,29,57 and at Days T2: 1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
Frequency of HBc-specific CD4+ T-cells	Frequency of HBc-specific CD4+ T-cells is expressed as HBc-specific CD4+ T-cells per million peripheral blood mononuclear cells (HBc-specific CD4+ T-cells/million PBMCs).	At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841
Frequency of HBs-specific CD4+ T-cells	Frequency of HBs-specific CD4+ T-cells is expressed as HBs-specific CD4+ T-cells/million PBMCs.	At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841
Frequency of HBc-specific CD8+ T-cells	Frequency of HBc-specific CD8+ T-cells is expressed as HBc-specific CD8+ T-cells/million PBMCs.	At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841
Frequency of HBs-specific CD8+ T-cells	Frequency of HBs-specific CD8+ T-cells is expressed as HBs-specific CD8+ T-cells/million PBMCs.	At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841
Number of HBc- and HBs-specific CD4+ T cells responders		At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841
Number of HBc- and HBs-specific CD8+ T cells responders		At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Estimated): February 11, 2026
• Study Completion (Estimated): February 11, 2026

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Immunogenicity; Reactogenicity; Hepatitis B virus; Chronic Hepatitis B; Chronic Hepatitis B targeted immunotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: 217023; 2021-003567-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No