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
NCT ID: NCT05276297
Last Updated: 2025-12-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
174 participants
INTERVENTIONAL
2022-03-22
2025-08-05
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
SINGLE
Study Groups
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Interventions
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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.
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.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
65 Years
ALL
No
Sponsors
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GlaxoSmithKline
INDUSTRY
Responsible Party
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Principal Investigators
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GSK Clinical Trials
Role: STUDY_DIRECTOR
GlaxoSmithKline
Locations
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GSK Investigational Site
Edegem, , Belgium
GSK Investigational Site
Sliven, , Bulgaria
GSK Investigational Site
Sofia, , Bulgaria
GSK Investigational Site
Sofia, , Bulgaria
GSK Investigational Site
Sofia, , Bulgaria
GSK Investigational Site
Sofia, , Bulgaria
GSK Investigational Site
Veliko Tarnovo, , Bulgaria
GSK Investigational Site
Vratsa, , Bulgaria
GSK Investigational Site
Clichy, , France
GSK Investigational Site
Créteil, , France
GSK Investigational Site
Lyon, , France
GSK Investigational Site
Strasbourg, , France
GSK Investigational Site
Berlin, , Germany
GSK Investigational Site
Frankfurt, , Germany
GSK Investigational Site
Leipzig, , Germany
GSK Investigational Site
Pokfulam, , Hong Kong
GSK Investigational Site
Bergamo, , Italy
GSK Investigational Site
Milan, , Italy
GSK Investigational Site
Milan, , Italy
GSK Investigational Site
Roma, , Italy
GSK Investigational Site
Rozzano MI, , Italy
GSK Investigational Site
Makati City, , Philippines
GSK Investigational Site
Pasig, , Philippines
GSK Investigational Site
Krakow, , Poland
GSK Investigational Site
Mysłowice, , Poland
GSK Investigational Site
Łańcut, , Poland
GSK Investigational Site
Cluj-Napoca, , Romania
GSK Investigational Site
Craiova Dolj, , Romania
GSK Investigational Site
Singapore, , Singapore
GSK Investigational Site
Singapore, , Singapore
GSK Investigational Site
Barcelona, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Santander, , Spain
GSK Investigational Site
Seville, , Spain
GSK Investigational Site
Vigo, , Spain
GSK Investigational Site
Chiayi City, , Taiwan
GSK Investigational Site
Kaohsiung City, , Taiwan
GSK Investigational Site
Linkou - Taoyuan Hsien, , Taiwan
GSK Investigational Site
Taichung, , Taiwan
GSK Investigational Site
Taichung, , Taiwan
GSK Investigational Site
Tainan, , Taiwan
GSK Investigational Site
Bangkok, , Thailand
GSK Investigational Site
Chiang Mai, , Thailand
GSK Investigational Site
Istanbul, , Turkey (Türkiye)
GSK Investigational Site
Rize, , Turkey (Türkiye)
GSK Investigational Site
Cottingham, , United Kingdom
GSK Investigational Site
Leicester, , United Kingdom
Countries
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Other Identifiers
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217023
Identifier Type: -
Identifier Source: org_study_id
2021-003567-10
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2024-512352-38-00
Identifier Type: CTIS
Identifier Source: secondary_id