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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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.
GSK Investigational Site
Boston, Massachusetts, United States
GSK Investigational Site
Toronto, Ontario, Canada
GSK Investigational Site
Rotterdam, Netherlands
GSK Investigational Site
London, United Kingdom
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
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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