A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
NCT Number: NCT06537414
Acronym: B-UNITED
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Chronic Hepatitis B Virus Infection
Interventions: DRUG: Daplusiran/Tomligisiran Dose Level 1|DRUG: Daplusiran/Tomligisiran Dose Level 2|DRUG: Bepirovirsen|DRUG: Placebo
Sponsor: GlaxoSmithKline
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 280
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-11-25
Completion Date: 2028-01-04

Summary:
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.

Primary Outcome Measures: Number of participants achieving functional cure, The functional cure for Hepatitis B virus (HBV) is defined as sustained suppression (24 weeks or longer) of HBV deoxyribonucleic acid (DNA) \<lower limit of quantification (LLOQ) off all HBV treatment and HBsAg not detected with or without Hepatitis B Surface Antibody (HBsAb) after a finite duration of therapy. The number of participants achieving functional cure after discontinuation of all chronic HBV treatments (DAP/TOM, bepirovirsen, and NA treatment) will be reported., Up to 100 Weeks
Secondary Outcome Measures: 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 off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy. 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., 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 off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy. 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., 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 off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy. 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., 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., Up to 48 Weeks