This study is intended to confirm the efficacy, safety, pharmacokinetic (PK) profile, and the durability of hepatitis B virus surface antigen (HBsAg) suppression observed with bepirovirsen for 24 weeks (with loading doses) as compared to the placebo arm. This study will have 4 stages: a) Double-blind treatment (bepirovirsen or placebo) for 24 weeks. b) Nucleos(t)ide analogue (NA) treatment for 24 weeks. c) NA cessation stage OR Continue NA for 24 weeks. d) Durability of response and follow up for further 24 weeks for participants who stopped NA treatment at Week 48. The arms will be stratified based on HBsAg level (HBsAg greater than or equal to \[≥\] 100 international unit per milliliter \[IU/mL\] to less than or equal \[≤\]1000 IU/mL or greater than \[\>\] 1000 IU/mL to ≤3000 IU/mL) at screening. The total duration of the study, including screening (up to 60 days), the double-blind treatment stage (24 weeks), the On NA only stage (24 weeks), and the NA cessation and durability stages (48 weeks) is up to approximately 104 weeks at maximum for each participant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
981
Bepirovirsen will be administered.
Matching placebo will be administered.
GSK Investigational Site
Chandler, Arizona, United States
GSK Investigational Site
Davis, California, United States
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Palo Alto, California, United States
GSK Investigational Site
San Jose, California, United States
Number of participants achieving functional cure (FC) with baseline HBsAg ≤3000 IU/mL
The number of participants who achieved FC after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported. The FC for HBV is defined as Sustained suppression (24 weeks or longer) of HBV DNA \< Lower limit of quantification (LLOQ) off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy.
Time frame: Up to 72 weeks
Number of participants achieving FC with baseline HBsAg ≤1000 IU/mL
The number of participants who achieved FC after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported. The FC for HBV is defined as Sustained suppression (24 weeks or longer) of HBV DNA (\<LLOQ) and HBsAg not detected with or without HBsAb after a finite duration of therapy.
Time frame: Up to 72 weeks
Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤3000 IU/mL
The number of participants who achieved sustained suppression of HBV DNA after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported.
Time frame: Up to 72 weeks
Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤1000 IU/mL
The number of participants who achieved sustained suppression of HBV DNA after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported.
Time frame: Up to 72 weeks
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GSK Investigational Site
Littleton, Colorado, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Iowa City, Iowa, United States
GSK Investigational Site
Baltimore, Maryland, United States
GSK Investigational Site
Detroit, Michigan, United States
...and 167 more locations