Hepatitis B
Conditions
Keywords
Hepatitis B virus, GSK3228836, Fine needle aspiration, Intrahepatic immunophenotyping
Brief summary
Hepatitis B virus (HBV) infection, especially chronic, is a significant worldwide medical problem. This is an exploratory study of the therapeutic mechanism of GSK3228836 in participants with chronic hepatitis B (CHB) on stable nucleos(t)ide therapy (which is the first line therapy for CHB). This study is a Phase IIa, multi-center open label exploratory study of the therapeutic mechanism of GSK3228836 in participants with hepatitis B virus e-antigen (HBeAg)-negative CHB on stable nucleos(t)ide therapy using repeat fine needle aspirations of the liver for intrahepatic immunophenotyping. It will investigate the virologic and immunologic correlates of hepatitis B virus surface antigen (HBsAg) loss observed in participants when treated for 12 weeks with 300 milligrams (mg) GSK3228836. Repeat fine needle aspirates of the liver will be performed to enable analysis of liver-resident immune cells to investigate any immunomodulatory properties of GSK3228836 and to study the biology of underlying treatment-associated liver flares. The study will consist of a screening, treatment, and post-treatment follow-up phase. Approximately 20 participants will be enrolled in the study.
Interventions
DRUGGSK3228836
GSK3228836 will be available as a clear colorless to slightly yellow solution for injection in 150 mg/milliliters (mL) vial to be administered SC once weekly.
Participants receiving nucleos(t)ide therapy upon entry in the study will continue to receive nucleos(t)ide therapy for the duration of the study.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single arm, multi-center, open label exploratory study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants should be at least 18 years of age at the time of signing the informed consent. * Participants who have documented chronic HBV infection \>=6 months prior to screening and currently receiving stable nucleos(t)ide analogue therapy, defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study. * Plasma or serum HBsAg concentration \>100 IU/mL * Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA \<90 IU/mL. * HBeAg-negative * ALT less than or equal to (\<=)2 times ULN * No gender restriction. * 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 i. Refrain from donating sperm ii. 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 1\) Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. * A female participant is eligible to participate: i. If she is not pregnant or breastfeeding. ii. and at least one of the following conditions applies: 1. Is not a WOCBP 2. 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 iii. A WOCBP must have both <!-- --> 1. 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) 2. and a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
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: 1. Current or past history of Hepatitis C virus (HCV) 2. Human immunodeficiency virus (HIV) 3. Hepatitis D virus (HDV). * History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by 1. Both Aspartate aminotransferase (AST)-Platelet Index (APRI) \>2 and FibroSure/FibroTest result \>0.7 1\) 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. 2. Regardless of APRI or Fibrosure/FibroTest score participants will be excluded from the study if their past history includes one of the following criteria: 1. Liver biopsy showing Metavir 4 or equivalent 2. Liver stiffness \>12 kilopascals (kPa) * Diagnosed or suspected hepatocellular carcinoma as evidenced by the following 1. Alpha-fetoprotein concentration \>=200 nanograms (ng)/mL 2. 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 enrolment. * 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 antibody (ANCA) at screening by itself won't be an exclusion criterion - but if results are borderline positive or positive: 1. Myeloperoxidase (MPO)-ANCA (perinuclear \[p\] ANCA) and Proteinase 3 (PR3)-ANCA (Cytoplasmic \[c\] ANCA) analysis will be conducted 2. 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 compliment (C)3 at screening or Baseline by itself won't be an exclusion criterion-but if it is present a. 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 1. Current alcohol use as judged by investigator to potentially interfere with participant compliance. 2. History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance. 1. 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 |
|---|---|---|
| Percentage of Participants Achieving Serum Hepatitis B Virus Surface Antigen (HBsAg) Level Less Than (<) Lower Limit of Quantitation (LLOQ) | Up to Week 12 | Percentage of participants achieving serum HBsAg level \<LLOQ were reported. Percentage values are rounded-off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment | Up to 24 weeks off treatment (Study Weeks 12 to 36) | Sustained virologic response is defined as HBsAg \<LLOQ and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \<LLOQ for 24 weeks from end of GSK3228836 treatment. Percentage values are rounded-off. |
| Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment (OT) Day 162 | Percentage of participants achieving HBsAg \<LLOQ were assessed at indicated time points. Percentage values are rounded-off. |
| Percentage of Participants Achieving HBV DNA <LLOQ at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment Day 162 | Percentage of participants achieving HBV DNA \<LLOQ were assessed at indicated time points. Percentage values are rounded-off. |
| Percentage of Participants Achieving HBsAg <LLOQ and HBV DNA <LLOQ at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment Day 162 | Percentage of participants achieving HBsAg \<LLOQ and HBV DNA \<LLOQ were assessed at indicated time points. Percentage values are rounded-off. |
| Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Baseline (Week -1), Treatment Week 12 and off treatment 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). The 'HBsAg \< LLOQ' category is derived based on Absolute/raw HBsAg result. The HBsAg decline categories are based on change from Baseline values. Percentage values are rounded-off. |
| Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Baseline (Week -1), treatment Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; off treatment Days 1, 8, 22, 50, 78, 106, 134 and 162 | Blood samples were collected at indicated time points to assess ALT levels. The ALT normalization (ALT \<=upper limit of normal \[ULN\]) over time in absence of rescue medication in participants with Baseline ALT\>ULN and ALT data at that visit. Participants who achieved ALT normalization were reported. |
| Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Baseline (Week -1), treatment Days 29, 36, and 57; off treatment Days 1, 8, 22, 50, 78, 106, 134 and 162 | Blood samples were collected to assess HBe antibody levels and results reported are for Baseline HBeAg positive participants. |
| Percentage of Participants With Sustained HBsAg Response (HBsAg <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment | Up to 24 weeks off treatment (Study Weeks 12 to 36) | Sustained HBsAg response is defined as HBsAg \<LLOQ for 24 weeks from end of GSK3228836 treatment. Percentage values are rounded-off. |
| Mean Change From Baseline in HBsAg at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment Day 162 | Blood samples were collected from participants at indicated time points to assess HBsAg levels. Change from Baseline was defined as value at the indicated time point minus Baseline value. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Actual Values of HBV DNA at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment Day 162 | Blood samples were collected from participants at indicated time points to assess HBV DNA levels. |
| Mean Change From Baseline in HBV DNA at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment Day 162 | Blood samples were collected from participants at indicated time points to assess HBV DNA levels. Change from Baseline was defined as value at the indicated time point minus Baseline value. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Actual Values of HB Surface Antibody (Anti-HBsAg) Levels at Indicated Time Points | Baseline (Week -1) and off treatment Days 1 and 162 | Blood samples were collected from participants at indicated time points to assess anti-HBsAg levels. |
| Area Under the Concentration-time Curve (AUC) for ALT at Indicated Time Points | Study Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 20, 24, 28, 32 and 36 | Blood samples were collected from participants to assess AUC for ALT. On-treatment blood samples were collected from Weeks 1 to 12 and follow-up blood samples were collected from Weeks 12 to 36. AUC was calculated and presented for on-treatment (12 Weeks), follow-up (24 weeks), and On-treatment + follow-up (Weeks 1 to 36). |
| Time to Maximum ALT | Up to Study Week 36 | Time to maximum ALT (maximum peak in ALT) during 36 week (treatment + follow-up) is defined as time from Baseline to the time of first peak in ALT. |
| Actual Values of HBsAg at Indicated Time Points | Baseline (Week -1), treatment Day 78 and off treatment Day 162 | Blood samples were collected from participants at indicated time points to assess HBsAg levels. |
Countries
Canada, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
This was an open label, single arm study to mechanistically interrogate the therapeutic effect of GSK3228836 in participants with Chronic Hepatitis B via intrahepatic immunophenotyping.
Pre-assignment details
A total of 12 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| GSK3228836 300 mg Participants on stable nucleos(t)ide therapy received GSK3228836 300 milligrams (mg) administered subcutaneously (SC) weekly once for 12 weeks along with a loading dose of GSK3228836 300 mg in Week 1 (Day 4) and Week 2 (Day 11). | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | GSK3228836 300 mg |
|---|---|
| Age, Continuous | 48.8 Years STANDARD_DEVIATION 8.48 |
| Race/Ethnicity, Customized De-identified | 12 Participants |
| Sex/Gender, Customized De-identified | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Percentage of Participants Achieving Serum Hepatitis B Virus Surface Antigen (HBsAg) Level Less Than (<) Lower Limit of Quantitation (LLOQ)
Percentage of participants achieving serum HBsAg level \<LLOQ were reported. Percentage values are rounded-off.
Time frame: Up to Week 12
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3228836 300 mg | Percentage of Participants Achieving Serum Hepatitis B Virus Surface Antigen (HBsAg) Level Less Than (<) Lower Limit of Quantitation (LLOQ) | 25 Percentage of participants |
Secondary
Actual Values of HBsAg at Indicated Time Points
Blood samples were collected from participants at indicated time points to assess HBsAg levels.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 300 mg | Actual Values of HBsAg at Indicated Time Points | Baseline (Week -1) | 3.29 Log10 IU/mL | Standard Deviation 0.59 |
| GSK3228836 300 mg | Actual Values of HBsAg at Indicated Time Points | Treatment Day 78 | 0.33 Log10 IU/mL | Standard Deviation 1.432 |
| GSK3228836 300 mg | Actual Values of HBsAg at Indicated Time Points | Off Treatment Day 162 | 2.08 Log10 IU/mL | Standard Deviation 1.933 |
Secondary
Actual Values of HB Surface Antibody (Anti-HBsAg) Levels at Indicated Time Points
Blood samples were collected from participants at indicated time points to assess anti-HBsAg levels.
Time frame: Baseline (Week -1) and off treatment Days 1 and 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 300 mg | Actual Values of HB Surface Antibody (Anti-HBsAg) Levels at Indicated Time Points | Baseline (Week -1) | 0.60 Log10 IU/mL | Standard Deviation 0 |
| GSK3228836 300 mg | Actual Values of HB Surface Antibody (Anti-HBsAg) Levels at Indicated Time Points | Off Treatment Day 1 | 0.71 Log10 IU/mL | Standard Deviation 0.238 |
| GSK3228836 300 mg | Actual Values of HB Surface Antibody (Anti-HBsAg) Levels at Indicated Time Points | Off Treatment Day 162 | 0.70 Log10 IU/mL | Standard Deviation 0.26 |
Secondary
Actual Values of HBV DNA at Indicated Time Points
Blood samples were collected from participants at indicated time points to assess HBV DNA levels.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 300 mg | Actual Values of HBV DNA at Indicated Time Points | Baseline (Week -1) | 0.43 Log10 IU/mL | Standard Deviation 0.849 |
| GSK3228836 300 mg | Actual Values of HBV DNA at Indicated Time Points | Treatment Day 78 | 0.31 Log10 IU/mL | Standard Deviation 0.611 |
| GSK3228836 300 mg | Actual Values of HBV DNA at Indicated Time Points | Off Treatment Day 162 | 0.24 Log10 IU/mL | Standard Deviation 0.525 |
Secondary
Area Under the Concentration-time Curve (AUC) for ALT at Indicated Time Points
Blood samples were collected from participants to assess AUC for ALT. On-treatment blood samples were collected from Weeks 1 to 12 and follow-up blood samples were collected from Weeks 12 to 36. AUC was calculated and presented for on-treatment (12 Weeks), follow-up (24 weeks), and On-treatment + follow-up (Weeks 1 to 36).
Time frame: Study Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 20, 24, 28, 32 and 36
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 300 mg | Area Under the Concentration-time Curve (AUC) for ALT at Indicated Time Points | On-Treatment (12 Weeks) | 494.75 Weeks*International Units Per Liter | Standard Deviation 562.593 |
| GSK3228836 300 mg | Area Under the Concentration-time Curve (AUC) for ALT at Indicated Time Points | Follow-up (24 weeks) | 650.58 Weeks*International Units Per Liter | Standard Deviation 462.762 |
| GSK3228836 300 mg | Area Under the Concentration-time Curve (AUC) for ALT at Indicated Time Points | On-Treatment + Follow-Up (Weeks 1 to 36) | 1173.72 Weeks*International Units Per Liter | Standard Deviation 836.768 |
Secondary
Mean Change From Baseline in HBsAg at Indicated Time Points
Blood samples were collected from participants at indicated time points to assess HBsAg levels. Change from Baseline was defined as value at the indicated time point minus Baseline value. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points. Participants who had Baseline and at least 1 post-Baseline visit values were included in analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 300 mg | Mean Change From Baseline in HBsAg at Indicated Time Points | Treatment Day 78 | -2.923 Log10 IU/mL | Standard Deviation 1.5803 |
| GSK3228836 300 mg | Mean Change From Baseline in HBsAg at Indicated Time Points | Off Treatment Day 162 | -1.183 Log10 IU/mL | Standard Deviation 1.8343 |
Secondary
Mean Change From Baseline in HBV DNA at Indicated Time Points
Blood samples were collected from participants at indicated time points to assess HBV DNA levels. Change from Baseline was defined as value at the indicated time point minus Baseline value. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points. Participants who had Baseline and at least 1 post-Baseline visit values were included in analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3228836 300 mg | Mean Change From Baseline in HBV DNA at Indicated Time Points | Treatment Day 78 | -0.271 Log10 IU/mL | Standard Deviation 1.1145 |
| GSK3228836 300 mg | Mean Change From Baseline in HBV DNA at Indicated Time Points | Off Treatment Day 162 | -0.237 Log10 IU/mL | Standard Deviation 0.7871 |
Secondary
Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points
Blood samples were collected at indicated time points to assess ALT levels. The ALT normalization (ALT \<=upper limit of normal \[ULN\]) over time in absence of rescue medication in participants with Baseline ALT\>ULN and ALT data at that visit. Participants who achieved ALT normalization were reported.
Time frame: Baseline (Week -1), treatment Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; off treatment Days 1, 8, 22, 50, 78, 106, 134 and 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. The n represents the number of participants with Baseline ALT \> ULN and ALT data at that visit. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Baseline (Week -1) | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 8 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 15 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 22 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 29 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 36 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 43 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 50 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 57 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 64 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 71 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Treatment Day 78 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 1 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 8 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 22 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 50 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 78 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 106 | 1 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 134 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points | Off Treatment Day 162 | 0 Participants |
Secondary
Number of Participants With HBe Antibody (Anti-HBeAg) Levels
Blood samples were collected to assess HBe antibody levels and results reported are for Baseline HBeAg positive participants.
Time frame: Baseline (Week -1), treatment Days 29, 36, and 57; off treatment Days 1, 8, 22, 50, 78, 106, 134 and 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Baseline (Week -1) | 11 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Treatment Day 29 | 11 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Treatment Day 36 | 0 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Treatment Day 57 | 9 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 1 | 9 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 8 | 10 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 22 | 10 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 50 | 10 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 78 | 10 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 106 | 10 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 134 | 8 Participants |
| GSK3228836 300 mg | Number of Participants With HBe Antibody (Anti-HBeAg) Levels | Off Treatment Day 162 | 10 Participants |
Secondary
Percentage of Participants Achieving HBsAg <LLOQ and HBV DNA <LLOQ at Indicated Time Points
Percentage of participants achieving HBsAg \<LLOQ and HBV DNA \<LLOQ were assessed at indicated time points. Percentage values are rounded-off.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3228836 300 mg | Percentage of Participants Achieving HBsAg <LLOQ and HBV DNA <LLOQ at Indicated Time Points | Baseline (Week -1) | 0 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving HBsAg <LLOQ and HBV DNA <LLOQ at Indicated Time Points | Treatment Day 78 | 20 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving HBsAg <LLOQ and HBV DNA <LLOQ at Indicated Time Points | Off Treatment Day 162 | 18 Percentage of participants |
Secondary
Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points
Percentage of participants achieving HBsAg \<LLOQ were assessed at indicated time points. Percentage values are rounded-off.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment (OT) Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3228836 300 mg | Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points | Baseline (Week -1) | 0 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points | Treatment Day 78 | 30 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points | Off Treatment Day 162 | 18 Percentage of participants |
Secondary
Percentage of Participants Achieving HBV DNA <LLOQ at Indicated Time Points
Percentage of participants achieving HBV DNA \<LLOQ were assessed at indicated time points. Percentage values are rounded-off.
Time frame: Baseline (Week -1), treatment Day 78 and off treatment Day 162
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3228836 300 mg | Percentage of Participants Achieving HBV DNA <LLOQ at Indicated Time Points | Baseline (Week -1) | 92 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving HBV DNA <LLOQ at Indicated Time Points | Treatment Day 78 | 78 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving HBV DNA <LLOQ at Indicated Time Points | Off Treatment Day 162 | 100 Percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment
Sustained virologic response is defined as HBsAg \<LLOQ and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \<LLOQ for 24 weeks from end of GSK3228836 treatment. Percentage values are rounded-off.
Time frame: Up to 24 weeks off treatment (Study Weeks 12 to 36)
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3228836 300 mg | Percentage of Participants Achieving Sustained Virologic Response (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment | Sustained Virologic Response for 24 Weeks after Planned End of GSK3228836 Treatment | 8 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants Achieving Sustained Virologic Response (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment | Sustained Virologic Response for 24 Weeks after Actual End of GSK3228836 Treatment | 8 Percentage of participants |
Secondary
Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points
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). The 'HBsAg \< LLOQ' category is derived based on Absolute/raw HBsAg result. The HBsAg decline categories are based on change from Baseline values. Percentage values are rounded-off.
Time frame: Baseline (Week -1), Treatment Week 12 and off treatment Week 24
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Treatment Week 12, HBsAg < LLOQ | 30 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Treatment Week 12, HBsAg decline <0.5 log10 IU/mL | 10 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Treatment Week 12, HBsAg decline >=0.5 log10 IU/mL | 90 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Treatment Week 12, HBsAg decline >=1 log10 IU/mL | 80 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Treatment Week 12, HBsAg decline >=1.5 log10 IU/mL | 80 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Treatment Week 12, HBsAg decline >=3 log10 IU/mL | 50 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Off Treatment Week 24, HBsAg < LLOQ | 18 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Off Treatment Week 24, HBsAg decline <0.5 log10 IU/mL | 73 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Off Treatment Week 24, HBsAg decline >=0.5 log10 IU/mL | 27 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Off Treatment Week 24, HBsAg decline >=1 log10 IU/mL | 27 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Off Treatment Week 24, HBsAg decline >=1.5 log10 IU/mL | 27 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points | Off Treatment Week 24, HBsAg decline >=3 log10 IU/mL | 18 Percentage of participants |
Secondary
Percentage of Participants With Sustained HBsAg Response (HBsAg <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment
Sustained HBsAg response is defined as HBsAg \<LLOQ for 24 weeks from end of GSK3228836 treatment. Percentage values are rounded-off.
Time frame: Up to 24 weeks off treatment (Study Weeks 12 to 36)
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3228836 300 mg | Percentage of Participants With Sustained HBsAg Response (HBsAg <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment | Sustained HBsAg Response for 24 Weeks after Planned End of GSK3228836 Treatment | 8 Percentage of participants |
| GSK3228836 300 mg | Percentage of Participants With Sustained HBsAg Response (HBsAg <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment | Sustained HBsAg Response for 24 Weeks after Actual End of GSK3228836 Treatment | 8 Percentage of participants |
Secondary
Time to Maximum ALT
Time to maximum ALT (maximum peak in ALT) during 36 week (treatment + follow-up) is defined as time from Baseline to the time of first peak in ALT.
Time frame: Up to Study Week 36
Population: Intent to Treat (ITT) Set that included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3228836 300 mg | Time to Maximum ALT | NA Weeks |