The study is intended to evaluate the efficacy and safety of 2 different doses of DAP/TOM followed by bepirovirsen in participants living with CHB on standard of care nucleos(t)ide analogue (NA) therapy. The study also aims to identify an optimal dose of DAP/TOM for sequenced therapy with bepirovirsen for further clinical development and to assess the contribution of DAP/TOM to the sequential regimen. The study will also include an optional long-term follow-up (LTFU) extension stage for eligible participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
283
Daplusiran/Tomligisiran dose level 1 will be administered
Daplusiran/Tomligisiran dose level 2 will be administered
Bepirovirsen will be administered
Placebo will be administered
GSK Investigational Site
San Francisco, California, United States
GSK Investigational Site
San Jose, California, United States
GSK Investigational Site
Minneapolis, Minnesota, United States
GSK Investigational Site
New York, New York, United States
GSK Investigational Site
Philadelphia, Pennsylvania, United States
Number of participants achieving functional cure
The functional cure for HBV is defined as sustained suppression (24 weeks or longer) of HBV deoxyribonucleic acid (DNA) \<lower limit of quantification (LLOQ) and HBsAg not detected with or without HBsAb after a finite duration of therapy and off all HBV treatment. The number of participants achieving functional cure after discontinuation of all chronic HBV treatments (DAP/TOM, bepirovirsen, and NA treatment) will be reported.
Time frame: Up to 100 Weeks
Number of participants achieving functional cure with high Baseline HBsAg level
The functional cure 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 and off all HBV treatment. The number of participants achieving functional cure with high Baseline HBsAg level after discontinuation of all chronic HBV treatments (DAP/TOM, bepirovirsen, and NA treatment) will be reported.
Time frame: Up to 100 Weeks
Number of participants achieving functional cure with low Baseline HBsAg level
The functional cure 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 and off all HBV treatment. The number of participants achieving functional cure with low Baseline HBsAg level after discontinuation of all chronic HBV treatments (DAP/TOM, bepirovirsen, and NA treatment) will be reported.
Time frame: Up to 100 Weeks
Number of participants achieving functional cure with low Baseline HBsAg level compared against placebo + bepirovirsen arm
The functional cure 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 and off all HBV treatment. The number of participants achieving functional cure with low Baseline HBsAg level after discontinuation of all chronic HBV treatments (DAP/TOM, bepirovirsen, and NA treatment) compared against placebo + bepirovirsen arm will be reported.
Time frame: Up to 100 Weeks
Number of participants with undetected HBsAg and HBV DNA <LLOQ
The number of participants with undetected HBsAg and HBV DNA \<LLOQ at the end of bepirovirsen treatment will be reported.
Time frame: Up to 48 Weeks
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GSK Investigational Site
Westmead, New South Wales, Australia
GSK Investigational Site
Fitzroy, Victoria, Australia
GSK Investigational Site
Brussels, Belgium
GSK Investigational Site
Edegem, Belgium
GSK Investigational Site
Ghent, Belgium
...and 70 more locations