A Study of GSK3228836 in Participants With Chronic Hepatitis B (CHB)

Hepatitis B Clinical Trial

— B-Clear  

Official title:

Phase IIb Multi-Center, Randomised, Partial-Blind Parallel Cohort Study to Assess the Efficacy and Safety of Treatment With GSK3228836 in Participants With Chronic Hepatitis B Virus (B-Clear)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04449029
• Other study ID #: 209668
• Status: Completed
• Phase: Phase 2
• Start date: July 27, 2020
• Est. completion date: March 18, 2022

Study information

• Verified date: April 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic hepatitis B virus (HBV) infection is a significant worldwide medical problem. GSK3228836 demonstrated target engagement in CHB participants who were not on treatment and in CHB participants on stable nucleos(t)ide therapy. This study is intended to evaluate if treatment with GSK3228836 can achieve sustained virologic response (SVR), that is hepatitis B virus surface antigen (HBsAg) less than (<) lower limit of quantitation (LLOQ) and HBV deoxyribonucleic acid (DNA) <LLOQ sustained for 24 weeks post-GSK3228836 treatment end. In addition, the study will also evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of GSK3228836 in the 4 dosing regimens. This study will assess the efficacy and safety of treatment with GSK3228836 in two populations of participants with CHB; participants on stable nucleos(t)ide treatment (Cohort 1) and participants who are not currently on nucleos(t)ide therapy (Cohort 2). For each population, participants will be randomized into one of the 4 different parallel arms to receive treatment. The study will consist of a screening, treatment, and post-treatment follow-up phase. Approximately, 440 participants will be enrolled in the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 457
• Est. completion date: March 18, 2022
• Est. primary completion date: March 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At least 18 years of age at the time of signing the informed consent.
• Participants who have documented chronic HBV infection greater than equal to (>=6) months prior to screening and not currently on nucleos(t)ide analogue therapy population defined as participants who never received HBV treatment (treatment naive) or must have ended nucleos(t)ide therapy at least 6 months prior to the screening visit; OR Currently receiving stable nucleos(t)ide analogue therapy population 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.
• Plasma or serum HBsAg concentration >100 international units per milliliter (IU/mL).
• Plasma or serum HBV DNA concentration: Participants not currently on nucleos(t)ide analogue therapy, plasma or serum HBV DNA >2000 IU/mL; Participants who are receiving stable nucleos(t)ide analogue therapy must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
• ALT for treatment naive participants and for participants who are not currently receiving treatment: ALT <3 times ULN will be included initially if agreed by the independent data monitoring committee (IDMC) after review of safety data, the ALT inclusion criteria may be expanded to include participants with ALT <5 times ULN; ALT less than equal to (<=2) times ULN for participants who are receiving stable nucleos(t)ide analogue therapy.
• Male and/or Female: A male participant is eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study treatment: 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 who is not currently pregnant. A female participant is eligible to participate: If she is not pregnant or breastfeeding AND at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent 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 both a confirmed menstrual period prior to the first dose of study intervention (additional evaluation [e.g., amenorrhea in athletes, birth control] should also be considered) and a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Capable of giving signed informed consent.

Exclusion Criteria:

• Clinically significant abnormalities, aside from chronic HBV infection in medical history (e.g., moderate-severe liver disease other than chronic HBV, acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis or coagulopathy) or physical examination.
• Co-infection with Current or past history of Hepatitis C virus (HCV), Human immunodeficiency virus (HIV), Hepatitis D virus (HDV).
• History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7. If only one parameter (APRI or FibroSure/FibroTest) result is positive, a discussion with the Medical Monitor is required before inclusion in study is permitted. Regardless of APRI of Fibrosure/FibroTest score, if the participant meets one of the following criteria, they will be excluded from the study: Liver biopsy (i.e., Metavir Score F4); Liver stiffness >12 kilopascals (kPa).
• Diagnosed or suspected hepatocellular carcinoma as evidenced by the following:

Alpha-fetoprotein concentration >=200 nanogram per milliliter (ng/mL); If the screening alpha fetoprotein concentration is >=50 ng/mL and <200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization.

• History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer). Participants under evaluation for possible malignancy are not eligible.
• History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause) or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
• History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
• Anti-neutrophil cytoplasmic antibodies (ANCA) at screening by itself won't be an exclusion criterion, but if results are borderline positive or positive: myeloperoxidase-ANCA (MPO-ANCA) (Perinuclear antineutrophil cytoplasmic antibodies [pANCA]) and proteinase 3- ANCA (PR3-ANCA) (Cytoplasmic antineutrophil cytoplasmic antibodies [cANCA]) analysis will be conducted; A discussion with the Medical Monitor will be required to review participant's complete medical history to ensure no past history or current manifestations of a vasculitic/inflammatory/auto-immune condition before inclusion in study is permitted.
• Low complement C3 (C3) at screening by itself won't be an exclusion criterion, but if it is present: A discussion with the Medical Monitor is required to review participant's complete medical history to ensure no past history or current manifestations of vasculitic/inflammatory/auto-immune conditions.
• History of alcohol or drug abuse/dependence: Current alcohol use as judged by investigator to potentially interfere with participant compliance; History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance. Refers to illicit drugs and substances with abuse potential. Medications that are used by the participant as directed, whether over-the-counter or through prescription, are acceptable and would not meet the exclusion criteria.
• Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (<=2 weeks) or topical/inhaled steroid use.
• Participants for whom immunosuppressive treatment is not advised, including therapeutic doses of steroids, will be excluded.
• Currently taking, or took within 12 months of screening, any interferon-containing therapy.
• Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors or anti-platelet agents like clopidogrel).
• The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study treatment (whichever is longer) or 90 days (if half-life or duration is unknown).
• Prior treatment with any oligonucleotide or small interfering ribonucleic acid (RNA) (Small interfering RNA [siRNA]) within 12 months prior to the first dosing day.
• Fridericia's QT correction formula (QTcF) >=450 milliseconds (msec) (if single electrocardiogram [ECG] at screening shows QTcF>=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).
• Laboratory results as follows: Serum albumin <3.5 grams per deciliter (g/dL), Glomerular filtration rate (GFR) <60 milliliter per minute per 1.73 square meter (mL/min /1.73 m^2) as calculated by the Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI) formula (for Japan, Japanese Society of Nephrology Chronic Kidney Disease Initiative [JSN-CKDI equation]), International normalized ratio (INR) >1.25. Platelet count <140 times 10^9 cells/L, Total bilirubin >1.25 times ULN. For participants with benign unconjugated hyperbilirubinemia with total bilirubin >1.25 times ULN, discussion for inclusion to the study is required with the Medical Monitor, Urine albumin to creatinine ratio (ACR) >=0.03 mg/mg (or >=30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement. In cases where participants have low urine albumin and low urine creatinine levels resulting in a urine ACR calculation >=0.03 mg/mg (or >=30 mg/g), the investigator should confirm that the participant does not have a history of diabetes, hypertension or other risk factors that may affect renal function and discuss with the Medical Monitor, or designee.
• History of/sensitivity to GSK3228836 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• GSK3228836
GSK3228836 will be available as a clear colorless to slightly yellow solution for injection at a unit dose strength of 150 mg/mL to be administered subcutaneously once weekly.
• Placebo
Placebo will be available as a clear colorless solution for injection to be administered subcutaneously once weekly.
• Nucleos(t)ide therapy
Participants receiving nucleos(t)ide therapy upon entry in the study will continue to receive nucleotide therapy for the duration of the study.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Bulgaria	GSK Investigational Site	Sliven
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Regina	Saskatchewan
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Victoria	British Columbia
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Chongqing	Sichuan
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Wuhan	Hubei
France	GSK Investigational Site	Clichy Cedex
France	GSK Investigational Site	Créteil cedex
France	GSK Investigational Site	Limoges cedex
France	GSK Investigational Site	Lyon cedex 04
France	GSK Investigational Site	Nice cedex 3
France	GSK Investigational Site	Strasbourg
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Hong Kong	GSK Investigational Site	Pokfulam
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Modena	Emilia-Romagna
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Ishikawa
Japan	GSK Investigational Site	Ishikawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Ulsan
Malaysia	GSK Investigational Site	Kuala Lumpur
Philippines	GSK Investigational Site	Makati City
Philippines	GSK Investigational Site	Quezon City
Poland	GSK Investigational Site	Lancut
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Myslowice
Poland	GSK Investigational Site	Warszawa
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Kaliningrad
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Krasnojarsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	St. Petersburg
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
South Africa	GSK Investigational Site	Durban	KwaZulu- Natal
South Africa	GSK Investigational Site	Ennerdale	Gauteng
South Africa	GSK Investigational Site	Kwaguqa Emalahleni	Mpumalanga
South Africa	GSK Investigational Site	Lenasia Johannesburg	Gauteng
South Africa	GSK Investigational Site	Port Elizabeth	Eastern Cape
South Africa	GSK Investigational Site	Vosloorus Ext 2
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda (Madrid)
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Sevilla
Taiwan	GSK Investigational Site	Changhua
Taiwan	GSK Investigational Site	Taichung
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiangmai
Thailand	GSK Investigational Site	Phitsanulok
Thailand	GSK Investigational Site	Songkla
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Newcastle-upon-Tyne
United Kingdom	GSK Investigational Site	Plymouth
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  China,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Philippines,  Poland,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  Thailand,  United Kingdom, 

References & Publications (1)

Yuen MF, Lim SG, Plesniak R, Tsuji K, Janssen HLA, Pojoga C, Gadano A, Popescu CP, Stepanova T, Asselah T, Diaconescu G, Yim HJ, Heo J, Janczewska E, Wong A, Idriz N, Imamura M, Rizzardini G, Takaguchi K, Andreone P, Arbune M, Hou J, Park SJ, Vata A, Cremer J, Elston R, Lukic T, Quinn G, Maynard L, Kendrick S, Plein H, Campbell F, Paff M, Theodore D; B-Clear Study Group. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022 Nov 24;387(21):1957-1968. doi: 10.1056/NEJMoa2210027. Epub 2022 Nov 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving Sustained Virologic Response (SVR)	The SVR was a composite endpoint defined as Hepatitis B surface antigen (HBsAg) and Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels were less than (<) Lower limit of quantitation (LLOQ) at the planned end of GSK3228836 treatment which is sustained for 24 weeks post-GSK3228836 treatment in the absence of rescue medication.	Up to Week 48
Secondary	Number of Participants Achieving HBsAg and HBV DNA<LLOQ	Participants achieving HBsAg and HBV DNA levels	Up to Week 26
Secondary	Number of Participants With Categorical Changes From Baseline in HBsAg Values	Participants who achieved a decline in HBsAg values from baseline were reported. Participants were categorized in the following categorical HBsAg decline of <0.5, greater than or equal to (>=) 0.5, >=1, >=1.5, and >=3 log10 international units per milliliter (IU/mL).	At Baseline and Week 24
Secondary	Number of Participants With Categorical Changes From Baseline in HBV DNA Values	Participants who achieved a decline in HBV DNA values from baseline were reported. Participants were categorized in the following categorical HBV DNA decline of <1, >=1, >=2, and >=3 log IU/mL.	At Baseline and Week 24
Secondary	Number of Participants With Alanine Aminotransferase (ALT) Normalization	The ALT normalization (ALT= upper limit of normal [ULN]) over time in absence of rescue medication in participants with baseline ALT>ULN.; Participants who achieved ALT normalization were reported.	At Baseline and Week 24
Secondary	Median Time to ALT Normalization	Time to ALT normalization (ALT=ULN) in the absence of rescue medication in participants with baseline ALT>ULN. Numbers of participants analyzed at Week 24 include participants with baseline ALT >ULN, and are as follows for NA therapy population: n=6 in GSK3228836 for 24 WK, n= 7 in GSK3228836 for 12 WK+12 WK, n=6 in GSK3228836 for 12 WK + Placebo for 12 WK, n=2 in Placebo for 12 WK + GSK3228836 for 12 WK, respectively. The numbers of participants analyzed are as follows for the not on NA therapy population: n=20 GSK3228836 for 24 WK, n=20 in GSK3228836 for 12 WK+12 WK, n=21 in GSK3228836 for 12 WK + Placebo for 12 WK, n=9 in Placebo for 12 WK + GSK3228836 for 12 WK arm, respectively.	Baseline and up to Week 48
Secondary	Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb)	Blood samples were collected to assess HBeAb level and participants with positive HBeAb were reported.	Up to Week 48
Secondary	Mean HBsAg and HBV DNA Level	Blood samples were collected from participants to assess HBsAg and HBV DNA level at indicated time points.	At Baseline, Week 12, and 24
Secondary	Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level	Blood samples were collected from participants to assess HBeAg level at indicated time points. Participants with presence of HBeAg at baseline were analyzed at indicated timepoint. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 U/mL = -0.03 log10 U/mL).	At Baseline, Week 12, and 24
Secondary	Mean Change From Baseline in HBsAg and HBV DNA Level	Blood samples were collected from participants to assess HBsAg and HBV DNA level at indicated time points. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 IU/mL = -0.03 log10 IU/mL).	At Baseline, Week 12, and 24
Secondary	Mean Change From Baseline in HBeAg Level	Blood samples were collected from participants to assess HBeAg level at indicated time points. Participants with presence of HBeAg at baseline were analyzed at indicated timepoint. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 U/mL = -0.03 log10 U/mL).	At Baseline, Week 12, and 24
Secondary	Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level	Blood samples were collected to assess anti-HBsAg level at indicated timepoints.	At Baseline, Week 36, and 48
Secondary	Mean Change From Baseline in Anti-HBsAg Level	Blood samples were collected to assess anti-HBsAg level at indicated timepoints.	At Baseline, Week 12, and 24
Secondary	Mean Area Under the Concentration-time Curve From Time 0 up to 24 Hours (AUC0-24h) of GSK3228836	Intensive pharmacokinetic (PK) sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h of GSK3228836.	Up to Week 24
Secondary	Mean Maximum Observed Concentration (Cmax) of GSK3228836	Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Cmax of GSK3228836.	Up to Week 24
Secondary	Median Time of Maximum Observed Concentration (Tmax) of GSK3228836	Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze tmax of GSK3228836.	Up to Week 24
Secondary	Mean AUC0-24h of NA Therapies	Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.	Up to Week 24
Secondary	Mean Ctau of NA Therapies	Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Ctau. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.	Up to Week 24
Secondary	Mean Cmax of NA Therapies	Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Cmax. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.	Up to Week 24
Secondary	Median Tmax of NA Therapies	Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze tmax. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.	Up to Week 24
Secondary	Median Terminal Half-life (t1/2) of GSK3228836	Blood samples were collected from all participants for t1/2 analysis of GSK3228836. Note: for this endpoint data for more comparable arms GSK3228836 for 24WK and 12+12 WK from both on NA and not on NA therapy were presented.	Up to Week 48
Secondary	Mean Ctau of GSK3228836	Blood samples were collected from all participants for Ctau analysis of GSK3228836 at indicated. Note: for this endpoint data for more comparable arms GSK3228836 for 24WK and 12+12 WK from both on NA and not on NA therapy were presented.	Up to Week 24