Hepatitis B
Conditions
Keywords
Chronic Hepatitis B, GSK3228836, Hepatitis B virus surface antigen, Nucleos(t)ide therapy, Sustained virologic response
Brief 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.
Interventions
DRUGGSK3228836
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.
DRUGPlacebo
Placebo will be available as a clear colorless solution for injection to be administered subcutaneously once weekly.
Participants receiving nucleos(t)ide therapy upon entry in the study will continue to receive nucleotide therapy for the duration of the study.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants will be blinded to the study treatment.
Intervention model description
Participants with CHB will be divided into two different cohorts; participants on stable nucleos(t)ide treatment and participants not currently on nucleos(t)ide therapy. For each cohort, participants will be randomized into one of the 4 different parallel arms to receive treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Sustained Virologic Response (SVR) | Up to Week 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Categorical Changes From Baseline in HBsAg Values | At Baseline and Week 24 | 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). |
| Number of Participants With Categorical Changes From Baseline in HBV DNA Values | At Baseline and Week 24 | 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. |
| Number of Participants With Alanine Aminotransferase (ALT) Normalization | At Baseline and Week 24 | 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. |
| Median Time to ALT Normalization | Baseline and up to Week 48 | 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. |
| Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | Up to Week 48 | Blood samples were collected to assess HBeAb level and participants with positive HBeAb were reported. |
| Mean HBsAg and HBV DNA Level | At Baseline, Week 12, and 24 | Blood samples were collected from participants to assess HBsAg and HBV DNA level at indicated time points. |
| Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | At Baseline, Week 12, and 24 | 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). |
| Mean Change From Baseline in HBsAg and HBV DNA Level | At Baseline, Week 12, and 24 | 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). |
| Mean Change From Baseline in HBeAg Level | At Baseline, Week 12, and 24 | 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). |
| Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Baseline, Week 36, and 48 | Blood samples were collected to assess anti-HBsAg level at indicated timepoints. |
| Number of Participants Achieving HBsAg and HBV DNA<LLOQ | Up to Week 26 | Participants achieving HBsAg and HBV DNA levels \<LLOQ at the end of treatment (EOT) were reported. |
| Mean Area Under the Concentration-time Curve From Time 0 up to 24 Hours (AUC0-24h) of GSK3228836 | Up to Week 24 | Intensive pharmacokinetic (PK) sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h of GSK3228836. |
| Mean Maximum Observed Concentration (Cmax) of GSK3228836 | Up to Week 24 | Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Cmax of GSK3228836. |
| Median Time of Maximum Observed Concentration (Tmax) of GSK3228836 | Up to Week 24 | Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze tmax of GSK3228836. |
| Mean AUC0-24h of NA Therapies | Up to Week 24 | 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. |
| Mean Ctau of NA Therapies | Up to Week 24 | 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. |
| Mean Cmax of NA Therapies | Up to Week 24 | 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. |
| Median Tmax of NA Therapies | Up to Week 24 | 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. |
| Median Terminal Half-life (t1/2) of GSK3228836 | Up to Week 48 | 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. |
| Mean Ctau of GSK3228836 | Up to Week 24 | 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. |
| Mean Change From Baseline in Anti-HBsAg Level | At Baseline, Week 12, and 24 | Blood samples were collected to assess anti-HBsAg level at indicated timepoints. |
Countries
Argentina, Bulgaria, Canada, China, France, Germany, Hong Kong, Italy, Japan, Malaysia, Philippines, Poland, Romania, Russia, Singapore, South Africa, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 457 participants were enrolled in the study. These 457 participants were from 2 different set of populations (referred here after as on nucleos(t)ide \[NA\] and not on NA therapy). Participants from these subpopulations were randomized in a ratio of 3:3:3:1 into 4 treatment arms for each population (total of 8 arms).
Participants by arm
| Arm | Count |
|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) All participants of this arm received 300 milligram (mg) GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11). | 68 |
| GSK3228836 for 12+12 WK (on NA Therapy) All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks. | 68 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks. | 68 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks. | 23 |
| GSK3228836 for 24 WK (Not on NA Therapy) All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11). | 70 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks. | 68 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks. | 68 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks. | 24 |
| Total | 457 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 1 | 1 | 5 | 1 | 4 | 0 |
Baseline characteristics
| Characteristic | GSK3228836 for 24 Weeks (WK) (on NA Therapy) | GSK3228836 for 12+12 WK (on NA Therapy) | GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | GSK3228836 for 24 WK (Not on NA Therapy) | GSK3228836 for 12+12 WK (Not on NA Therapy) | GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.0 YEARS STANDARD_DEVIATION 11.54 | 46.1 YEARS STANDARD_DEVIATION 12.6 | 47.4 YEARS STANDARD_DEVIATION 11.18 | 49.8 YEARS STANDARD_DEVIATION 11.21 | 44.5 YEARS STANDARD_DEVIATION 11.1 | 43.8 YEARS STANDARD_DEVIATION 9.92 | 40.7 YEARS STANDARD_DEVIATION 11.1 | 42.4 YEARS STANDARD_DEVIATION 12.02 | 42.9 YEARS STANDARD_DEVIATION 10.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 36 Participants | 35 Participants | 36 Participants | 12 Participants | 37 Participants | 44 Participants | 38 Participants | 12 Participants | 250 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 4 Participants | 0 Participants | 9 Participants | 4 Participants | 6 Participants | 1 Participants | 27 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 30 Participants | 32 Participants | 26 Participants | 11 Participants | 24 Participants | 20 Participants | 24 Participants | 11 Participants | 178 Participants |
| Sex: Female, Male Female | 20 Participants | 19 Participants | 17 Participants | 6 Participants | 37 Participants | 27 Participants | 29 Participants | 13 Participants | 168 Participants |
| Sex: Female, Male Male | 48 Participants | 49 Participants | 51 Participants | 17 Participants | 33 Participants | 41 Participants | 39 Participants | 11 Participants | 289 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 67 | 0 / 68 | 0 / 23 | 0 / 70 | 0 / 67 | 0 / 68 | 0 / 24 |
| other Total, other adverse events | 56 / 68 | 59 / 67 | 53 / 68 | 16 / 23 | 65 / 70 | 60 / 67 | 61 / 68 | 19 / 24 |
| serious Total, serious adverse events | 1 / 68 | 1 / 67 | 4 / 68 | 0 / 23 | 6 / 70 | 2 / 67 | 3 / 68 | 0 / 24 |
Outcome results
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.
Time frame: Up to Week 48
Population: The analysis was performed on the Intent to Treat (ITT) Set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 6 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 6 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 2 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 0 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 7 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 4 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 1 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants Achieving Sustained Virologic Response (SVR) | 0 Participants |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK Set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Area Under the Concentration-time Curve From Time 0 up to 24 Hours (AUC0-24h) of GSK3228836 | 55.214 hour*micrograms per milliliter (h*ug/mL) | Standard Deviation 22.9901 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Area Under the Concentration-time Curve From Time 0 up to 24 Hours (AUC0-24h) of GSK3228836 | 140.312 hour*micrograms per milliliter (h*ug/mL) | Standard Deviation 37.3548 |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK Set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean AUC0-24h of NA Therapies | 2753.908 h*nanograms per milliliter (h*ng/mL) | Standard Deviation 661.3392 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean AUC0-24h of NA Therapies | 308.167 h*nanograms per milliliter (h*ng/mL) | Standard Deviation 104.8297 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean AUC0-24h of NA Therapies | 24.43 h*nanograms per milliliter (h*ng/mL) | Standard Deviation 6.761 |
Secondary
Mean Change From Baseline in Anti-HBsAg Level
Blood samples were collected to assess anti-HBsAg level at indicated timepoints.
Time frame: At Baseline, Week 12, and 24
Population: The analysis was performed on ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment participant was randomized to. One participant from 12+12 weeks on NA therapy arm who was randomized in error is in ITT population but did not contribute any lab data so is not part of the analysis. Four participants across other arms had missing anti-HBsAg baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.67 Log10 IU/mL | Standard Deviation 0.289 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.22 Log10 IU/mL | Standard Deviation 0.429 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.28 Log10 IU/mL | Standard Deviation 0.481 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.12 Log10 IU/mL | Standard Deviation 0.335 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.18 Log10 IU/mL | Standard Deviation 0.343 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.65 Log10 IU/mL | Standard Deviation 0.165 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.07 Log10 IU/mL | Standard Deviation 0.267 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.64 Log10 IU/mL | Standard Deviation 0.129 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.11 Log10 IU/mL | Standard Deviation 0.319 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.66 Log10 IU/mL | Standard Deviation 0.287 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.13 Log10 IU/mL | Standard Deviation 0.25 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.09 Log10 IU/mL | Standard Deviation 0.239 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.37 Log10 IU/mL | Standard Deviation 0.615 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.65 Log10 IU/mL | Standard Deviation 0.284 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.26 Log10 IU/mL | Standard Deviation 0.507 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.13 Log10 IU/mL | Standard Deviation 0.353 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.69 Log10 IU/mL | Standard Deviation 0.303 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.10 Log10 IU/mL | Standard Deviation 0.319 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.12 Log10 IU/mL | Standard Deviation 0.221 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.62 Log10 IU/mL | Standard Deviation 0.15 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.09 Log10 IU/mL | Standard Deviation 0.203 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Baseline | 0.74 Log10 IU/mL | Standard Deviation 0.307 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 12 | 0.16 Log10 IU/mL | Standard Deviation 0.355 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in Anti-HBsAg Level | At Week 24 | 0.09 Log10 IU/mL | Standard Deviation 0.203 |
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).
Time frame: At Baseline, Week 12, and 24
Population: The analysis was performed on the ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 0.49 Log u/mL | Standard Deviation 1.014 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -0.85 Log u/mL | Standard Deviation 1.071 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.52 Log u/mL | Standard Deviation 0.874 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -0.56 Log u/mL | Standard Deviation 0.811 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.42 Log u/mL | Standard Deviation 0.48 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 0.12 Log u/mL | Standard Deviation 0.756 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -0.46 Log u/mL | Standard Deviation 0.595 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 0.36 Log u/mL | Standard Deviation 1.053 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.33 Log u/mL | Standard Deviation 0.343 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 0.63 Log u/mL | Standard Deviation 1.323 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.17 Log u/mL | Standard Deviation 0.453 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -0.56 Log u/mL | Standard Deviation 0.598 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.65 Log u/mL | Standard Deviation 0.919 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 2.13 Log u/mL | Standard Deviation 1.564 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -1.01 Log u/mL | Standard Deviation 1.426 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -1.25 Log u/mL | Standard Deviation 1.522 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 2.52 Log u/mL | Standard Deviation 0.919 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -1.18 Log u/mL | Standard Deviation 1.532 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.94 Log u/mL | Standard Deviation 1.618 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 1.77 Log u/mL | Standard Deviation 1.612 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -0.70 Log u/mL | Standard Deviation 1.673 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Baseline | 2.84 Log u/mL | Standard Deviation 0.743 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at Week 12 | -0.14 Log u/mL | Standard Deviation 0.313 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBeAg Level | HBeAg, at WeeK 24 | -1.78 Log u/mL | Standard Deviation 2.057 |
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).
Time frame: At Baseline, Week 12, and 24
Population: The analysis was performed on ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment participant was randomized to. One participant from 12+12 weeks on NA therapy arm who was randomized in error is in ITT population but did not contribute any lab data so is not part of the analysis. One participant from 12+12 weeks not on NA therapy has no baseline data due to insufficient sample quantity at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.06 log IU/mL | Standard Deviation 0.831 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.29 log IU/mL | Standard Deviation 0.623 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -2.09 log IU/mL | Standard Deviation 1.649 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -2.62 log IU/mL | Standard Deviation 1.653 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.24 log IU/mL | Standard Deviation 0.793 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.29 log IU/mL | Standard Deviation 0.623 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -1.81 log IU/mL | Standard Deviation 1.488 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.26 log IU/mL | Standard Deviation 0.608 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.26 log IU/mL | Standard Deviation 0.608 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.17 log IU/mL | Standard Deviation 0.661 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -2.23 log IU/mL | Standard Deviation 1.597 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.47 log IU/mL | Standard Deviation 0.773 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.16 log IU/mL | Standard Deviation 0.942 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -0.83 log IU/mL | Standard Deviation 1.248 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -1.59 log IU/mL | Standard Deviation 1.474 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.33 log IU/mL | Standard Deviation 0.588 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.09 log IU/mL | Standard Deviation 0.928 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.33 log IU/mL | Standard Deviation 0.588 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.19 log IU/mL | Standard Deviation 0.727 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.43 log IU/mL | Standard Deviation 0.435 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -0.03 log IU/mL | Standard Deviation 0.089 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -2.57 log IU/mL | Standard Deviation 1.671 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.43 log IU/mL | Standard Deviation 0.435 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.33 log IU/mL | Standard Deviation 0.928 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | -1.96 log IU/mL | Standard Deviation 1.365 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -2.37 log IU/mL | Standard Deviation 1.585 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | -2.66 log IU/mL | Standard Deviation 1.646 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.72 log IU/mL | Standard Deviation 0.771 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.72 log IU/mL | Standard Deviation 0.771 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -2.96 log IU/mL | Standard Deviation 1.656 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -1.77 log IU/mL | Standard Deviation 1.489 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.64 log IU/mL | Standard Deviation 0.721 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -2.41 log IU/mL | Standard Deviation 1.562 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | -2.22 log IU/mL | Standard Deviation 1.592 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.64 log IU/mL | Standard Deviation 0.721 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | -2.2 log IU/mL | Standard Deviation 1.68 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.66 log IU/mL | Standard Deviation 0.675 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | -1.92 log IU/mL | Standard Deviation 1.349 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.66 log IU/mL | Standard Deviation 0.675 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -0.77 log IU/mL | Standard Deviation 1.108 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | -1.52 log IU/mL | Standard Deviation 1.637 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -2.06 log IU/mL | Standard Deviation 1.638 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Baseline | 3.76 log IU/mL | Standard Deviation 0.789 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 24 | -2.09 log IU/mL | Standard Deviation 1.764 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 24 | -2.6 log IU/mL | Standard Deviation 2.001 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBV DNA, at Week 12 | -0.54 log IU/mL | Standard Deviation 1.421 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.76 log IU/mL | Standard Deviation 0.789 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Change From Baseline in HBsAg and HBV DNA Level | HBsAg, at Week 12 | -0.08 log IU/mL | Standard Deviation 0.292 |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Cmax of NA Therapies | 318.857 ng/mL | Standard Deviation 95.94 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Cmax of NA Therapies | 19.36 ng/mL | Standard Deviation 5.85 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Cmax of NA Therapies | 6.526 ng/mL | Standard Deviation 2.27 |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 8 | 21.009 ng/mL | Standard Deviation 9.6214 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 24 | 31.102 ng/mL | Standard Deviation 28.7535 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 12 | 23.162 ng/mL | Standard Deviation 11.8963 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 8 | 47.039 ng/mL | Standard Deviation 198.1345 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 24 | 18.95 ng/mL | Standard Deviation 14.6513 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 12 | 23.234 ng/mL | Standard Deviation 11.6993 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 12 | 21.777 ng/mL | Standard Deviation 9.9248 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 8 | 21.663 ng/mL | Standard Deviation 14.4479 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 24 | 28.158 ng/mL | Standard Deviation 17.0606 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 8 | 23.46 ng/mL | Standard Deviation 16.6498 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 24 | 20.138 ng/mL | Standard Deviation 19.023 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Ctau of GSK3228836 | At Week 12 | 22.789 ng/mL | Standard Deviation 11.7361 |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK Set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Ctau of NA Therapies | 57.04 ng/mL | Standard Deviation 17.0787 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Ctau of NA Therapies | 10.31 ng/mL | Standard Deviation 3.4802 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Ctau of NA Therapies | 0.478 ng/mL | Standard Deviation 0.1055 |
Secondary
Mean HBsAg and HBV DNA Level
Blood samples were collected from participants to assess HBsAg and HBV DNA level at indicated time points.
Time frame: At Baseline, Week 12, and 24
Population: The analysis was performed on ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment participant was randomized to. One participant from 12+12 weeks on NA therapy arm who was randomized in error is in ITT population but did not contribute any lab data so is not part of the analysis. One participant from 12+12 weeks not on NA therapy has no baseline data due to insufficient sample quantity at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 0.48 Log10 (IU/mL) | Standard Deviation 0.638 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.55 Log10 (IU/mL) | Standard Deviation 0.654 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 1.20 Log10 (IU/mL) | Standard Deviation 1.878 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 0.65 Log10 (IU/mL) | Standard Deviation 1.939 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.29 Log10 (IU/mL) | Standard Deviation 0.623 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.74 Log10 (IU/mL) | Standard Deviation 0.654 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 1.45 Log10 (IU/mL) | Standard Deviation 1.809 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.26 Log10 (IU/mL) | Standard Deviation 0.608 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 0.39 Log10 (IU/mL) | Standard Deviation 0.603 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.56 Log10 (IU/mL) | Standard Deviation 0.649 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 1.04 Log10 (IU/mL) | Standard Deviation 1.858 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.86 Log10 (IU/mL) | Standard Deviation 0.7 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.67 Log10 (IU/mL) | Standard Deviation 0.785 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 2.51 Log10 (IU/mL) | Standard Deviation 1.536 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.56 Log10 (IU/mL) | Standard Deviation 0.714 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 0.53 Log10 (IU/mL) | Standard Deviation 0.659 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.33 Log10 (IU/mL) | Standard Deviation 0.588 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 1.76 Log10 (IU/mL) | Standard Deviation 1.706 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 0.61 Log10 (IU/mL) | Standard Deviation 0.682 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.43 Log10 (IU/mL) | Standard Deviation 0.435 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 3.36 Log10 (IU/mL) | Standard Deviation 0.431 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 0.83 Log10 (IU/mL) | Standard Deviation 1.801 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 0.40 Log10 (IU/mL) | Standard Deviation 0.622 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 0.79 Log10 (IU/mL) | Standard Deviation 0.667 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 3.00 Log10 (IU/mL) | Standard Deviation 2.242 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 1.39 Log10 (IU/mL) | Standard Deviation 1.965 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 2.37 Log10 (IU/mL) | Standard Deviation 2.137 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.72 Log10 (IU/mL) | Standard Deviation 0.771 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 5.02 Log10 (IU/mL) | Standard Deviation 1.527 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 0.77 Log10 (IU/mL) | Standard Deviation 2.016 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 1.88 Log10 (IU/mL) | Standard Deviation 1.915 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 5.14 Log10 (IU/mL) | Standard Deviation 1.557 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 1.27 Log10 (IU/mL) | Standard Deviation 2 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.64 Log10 (IU/mL) | Standard Deviation 0.721 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 2.92 Log10 (IU/mL) | Standard Deviation 2.142 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 2.93 Log10 (IU/mL) | Standard Deviation 2.317 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 4.67 Log10 (IU/mL) | Standard Deviation 1.497 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 2.88 Log10 (IU/mL) | Standard Deviation 1.511 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 2.68 Log10 (IU/mL) | Standard Deviation 1.996 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 3.07 Log10 (IU/mL) | Standard Deviation 1.938 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.66 Log10 (IU/mL) | Standard Deviation 0.675 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 1.57 Log10 (IU/mL) | Standard Deviation 1.808 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Baseline | 5.57 Log10 (IU/mL) | Standard Deviation 1.654 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 24 | 3.04 Log10 (IU/mL) | Standard Deviation 2.224 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 24 | 1.64 Log10 (IU/mL) | Standard Deviation 2.171 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBV DNA, at Week 12 | 4.96 Log10 (IU/mL) | Standard Deviation 2.074 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Baseline | 3.76 Log10 (IU/mL) | Standard Deviation 0.789 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean HBsAg and HBV DNA Level | HBsAg, at Week 12 | 3.68 Log10 (IU/mL) | Standard Deviation 0.798 |
Secondary
Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level
Blood samples were collected to assess anti-HBsAg level at indicated timepoints.
Time frame: At Baseline, Week 36, and 48
Population: The analysis was performed on ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment participant was randomized to. One participant from 12+12 weeks on NA therapy arm who was randomized in error is in ITT population but did not contribute any lab data so is not part of the analysis. Four participants across other arms had missing anti-HBsAg baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.67 Log10 IU/mL | Standard Deviation 0.289 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.88 Log10 IU/mL | Standard Deviation 0.471 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.94 Log10 IU/mL | Standard Deviation 0.534 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.77 Log10 IU/mL | Standard Deviation 0.368 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.83 Log10 IU/mL | Standard Deviation 0.401 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.65 Log10 IU/mL | Standard Deviation 0.165 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.70 Log10 IU/mL | Standard Deviation 0.277 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.64 Log10 IU/mL | Standard Deviation 0.129 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.74 Log10 IU/mL | Standard Deviation 0.333 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.66 Log10 IU/mL | Standard Deviation 0.287 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.79 Log10 IU/mL | Standard Deviation 0.368 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.75 Log10 IU/mL | Standard Deviation 0.326 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 1.01 Log10 IU/mL | Standard Deviation 0.66 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.65 Log10 IU/mL | Standard Deviation 0.284 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.91 Log10 IU/mL | Standard Deviation 0.567 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.82 Log10 IU/mL | Standard Deviation 0.385 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.69 Log10 IU/mL | Standard Deviation 0.303 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.79 Log10 IU/mL | Standard Deviation 0.369 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.74 Log10 IU/mL | Standard Deviation 0.347 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.62 Log10 IU/mL | Standard Deviation 0.15 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.71 Log10 IU/mL | Standard Deviation 0.296 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At baseline | 0.74 Log10 IU/mL | Standard Deviation 0.307 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 36 | 0.90 Log10 IU/mL | Standard Deviation 0.437 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level | At Week 48 | 0.83 Log10 IU/mL | Standard Deviation 0.356 |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK Set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Maximum Observed Concentration (Cmax) of GSK3228836 | 6.112 ug/mL | Standard Deviation 2.8112 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Maximum Observed Concentration (Cmax) of GSK3228836 | 14.956 ug/mL | Standard Deviation 5.6592 |
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).
Time frame: At Baseline, Week 12, and 24
Population: The analysis was performed on the ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 0.49 Log10 unit per milliliter (U/mL) | Standard Deviation 1.014 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | -0.41 Log10 unit per milliliter (U/mL) | Standard Deviation 0.635 |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 0.06 Log10 unit per milliliter (U/mL) | Standard Deviation 1.027 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | -0.48 Log10 unit per milliliter (U/mL) | Standard Deviation 0.752 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | -0.21 Log10 unit per milliliter (U/mL) | Standard Deviation 0.732 |
| GSK3228836 for 12+12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 0.12 Log10 unit per milliliter (U/mL) | Standard Deviation 0.756 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | -0.19 Log10 unit per milliliter (U/mL) | Standard Deviation 1.071 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 0.36 Log10 unit per milliliter (U/mL) | Standard Deviation 1.053 |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 0.19 Log10 unit per milliliter (U/mL) | Standard Deviation 1.089 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 0.63 Log10 unit per milliliter (U/mL) | Standard Deviation 1.323 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 0.60 Log10 unit per milliliter (U/mL) | Standard Deviation 1.31 |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | 0.08 Log10 unit per milliliter (U/mL) | Standard Deviation 1.497 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 1.84 Log10 unit per milliliter (U/mL) | Standard Deviation 1.805 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 2.13 Log10 unit per milliliter (U/mL) | Standard Deviation 1.564 |
| GSK3228836 for 24 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | 1.18 Log10 unit per milliliter (U/mL) | Standard Deviation 2.064 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 1.52 Log10 unit per milliliter (U/mL) | Standard Deviation 1.831 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 2.52 Log10 unit per milliliter (U/mL) | Standard Deviation 0.919 |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | 1.34 Log10 unit per milliliter (U/mL) | Standard Deviation 1.936 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 1.07 Log10 unit per milliliter (U/mL) | Standard Deviation 1.551 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 1.77 Log10 unit per milliliter (U/mL) | Standard Deviation 1.612 |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | 0.89 Log10 unit per milliliter (U/mL) | Standard Deviation 1.667 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Baseline | 2.84 Log10 unit per milliliter (U/mL) | Standard Deviation 0.743 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 12 | 2.79 Log10 unit per milliliter (U/mL) | Standard Deviation 0.725 |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level | HBeAg, at Week 24 | 1.06 Log10 unit per milliliter (U/mL) | Standard Deviation 2.165 |
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.
Time frame: Up to Week 48
Population: The analysis was performed on the PK set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Median Terminal Half-life (t1/2) of GSK3228836 | 28.897 Day |
| GSK3228836 for 12+12 WK (on NA Therapy) | Median Terminal Half-life (t1/2) of GSK3228836 | 24.918 Day |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Median Terminal Half-life (t1/2) of GSK3228836 | 27.846 Day |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Median Terminal Half-life (t1/2) of GSK3228836 | 38.205 Day |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK Set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Median Time of Maximum Observed Concentration (Tmax) of GSK3228836 | 3.008 hour |
| GSK3228836 for 12+12 WK (on NA Therapy) | Median Time of Maximum Observed Concentration (Tmax) of GSK3228836 | 3.017 hour |
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.
Time frame: Baseline and up to Week 48
Population: The analysis was performed on the ITT Set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations. Only those participants with baseline ALT\>ULN were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Median Time to ALT Normalization | 16.6 Weeks |
| GSK3228836 for 12+12 WK (on NA Therapy) | Median Time to ALT Normalization | 4.1 Weeks |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Median Time to ALT Normalization | 1 Weeks |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Median Time to ALT Normalization | 7 Weeks |
| GSK3228836 for 24 WK (Not on NA Therapy) | Median Time to ALT Normalization | 13.4 Weeks |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Median Time to ALT Normalization | 15.1 Weeks |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Median Time to ALT Normalization | 10.7 Weeks |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Median Time to ALT Normalization | 18.1 Weeks |
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.
Time frame: Up to Week 24
Population: The analysis was performed on the PK set that includes all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Median Tmax of NA Therapies | 1 hour |
| GSK3228836 for 12+12 WK (on NA Therapy) | Median Tmax of NA Therapies | 1.417 hour |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Median Tmax of NA Therapies | 0.983 hour |
Secondary
Number of Participants Achieving HBsAg and HBV DNA<LLOQ
Participants achieving HBsAg and HBV DNA levels \<LLOQ at the end of treatment (EOT) were reported.
Time frame: Up to Week 26
Population: The analysis was performed on the ITT Set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 16 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 9 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 8 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 4 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 17 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 10 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 6 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants Achieving HBsAg and HBV DNA<LLOQ | 1 Participants |
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.
Time frame: At Baseline and Week 24
Population: The analysis was performed on the ITT Set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 3 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 6 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 7 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 6 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 6 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 5 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 2 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 0 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 10 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 20 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 20 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 11 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 21 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 8 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT normalization, at Week 24 | 5 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Participants with ALT > ULN, at Baseline | 9 Participants |
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).
Time frame: At Baseline and Week 24
Population: The analysis was performed on the ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations. One participant from 12+12 weeks on NA therapy arm was randomized in error and is in ITT population but did not contribute any lab data so is not part of the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 34 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 12 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 52 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 42 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 48 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 42 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 38 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 16 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 21 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 32 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 12 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 20 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 37 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 14 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 5 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 15 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 4 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 17 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 17 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 10 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 48 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 8 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 35 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 51 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 55 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 48 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 36 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 14 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 30 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 13 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 18 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 9 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 22 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 4 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 29 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1 log10 IU/mL | 15 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=0.5 log10 IU/mL | 15 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=3 log10 IU/mL | 9 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline >=1.5 log10 IU/mL | 12 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg< LLOQ, at baseline | 0 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBsAg Values | HBsAg decline <0.5 log10 IU/mL | 8 Participants |
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.
Time frame: At Baseline and Week 24
Population: The analysis was performed on ITT set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment participant was randomized to. One participant from 12+12 weeks on NA therapy arm who was randomized in error is in ITT population but did not contribute any lab data so is not part of the analysis. One participant from 12+12 weeks not on NA therapy has no baseline data due to insufficient sample quantity at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 66 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 0 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 0 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 11 Participants |
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 2 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 0 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 0 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 0 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 4 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 66 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 0 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 0 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 66 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 0 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 13 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 3 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 0 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 22 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 0 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 0 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 51 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 0 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 3 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 40 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 27 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 44 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 23 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 12 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 0 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 19 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 30 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 0 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 21 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 11 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 19 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=3 log10 IU/mL | 9 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=2 log10 IU/mL | 14 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA < LLOQ, at Baseline | 0 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline >=1 log10 IU/mL | 18 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Categorical Changes From Baseline in HBV DNA Values | HBV DNA decline <1 log10 IU/mL | 3 Participants |
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.
Time frame: Up to Week 48
Population: The analysis was performed on the ITT Set that includes all randomized participants who received a treatment randomization number. This population was based on the treatment the participant was randomized to. The analysis was conducted separately for the on NA treatment and not currently on NA treatment populations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3228836 for 24 Weeks (WK) (on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 3 Participants |
| GSK3228836 for 12+12 WK (on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 4 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 5 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 2 Participants |
| GSK3228836 for 24 WK (Not on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 6 Participants |
| GSK3228836 for 12+12 WK (Not on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 4 Participants |
| GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 6 Participants |
| Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy) | Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) | 3 Participants |