Chronic Hepatitis B Virus Infection, Hepatitis B
Conditions
Keywords
Bepirovirsen, B-UNITED, Daplusiran/Tomligisiran, Hepatitis B, Nucleos(t)ide analogue
Brief 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. The study will also include an optional long-term follow-up (LTFU) extension stage for eligible participants.
Interventions
DRUGDaplusiran/Tomligisiran Dose Level 1
Daplusiran/Tomligisiran dose level 1 will be administered
DRUGDaplusiran/Tomligisiran Dose Level 2
Daplusiran/Tomligisiran dose level 2 will be administered
DRUGBepirovirsen
Bepirovirsen will be administered
DRUGPlacebo
Placebo will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age: At least 18 years of age at the time of signing the informed consent * Documented chronic HBV infection greater than or equal to (\>=) 6 months prior to Screening AND currently receiving stable NA therapy defined as receiving an NA regimen form at least 6 months prior to Screening and with no planned changes to their stable regimen over the duration of the study. * Plasma or serum HBsAg concentration greater than (\>) 100 international units per milliliter (IU/mL) * Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA less than (\<) 90 IU/mL * Alanine aminotransferase less than or equal to (\<=) 2\* upper limit of normal (ULN) * Participants who are willing and able to cease their NA treatment in accordance with the protocol. * Male and Female
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 coagulopathy) or clinically significant physical examination findings. * Coinfection with Hepatitis C (cured \<12 months at the time of screening), Human immunodeficiency virus or hepatitis D virus * History of or suspected liver cirrhosis and/or evidence of cirrhosis. * Diagnosed or suspected hepatocellular carcinoma. * History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (example, 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), current or history of an autoimmune condition or history/presence of other diseases that may be associated with vasculitis condition (example, systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex). * History of extrahepatic disorders possibly related to HBV immune conditions (example, nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension). * History of alcohol or drug abuse/dependence: * Currently taking, or took within 3 months of screening, any immunosuppressing drugs (example, prednisone), other than a short course of therapy (\<=2 weeks) or topical/inhaled steroid use. * Participants, to whom immunosuppressive treatment (including therapeutic doses of steroids) is contraindicated, should not be considered for enrollment in the study. * Currently taking, or has taken within 6 months of Screening, any interferon-containing therapy. * Participants requiring anti-coagulation therapies (example, warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of Investigational medicinal product (IMP) treatment, by the discretion of the investigator. Occasional use is permitted. * Prior hepatitis B treatment with bepirovirsen, DAP/TOM, or another oligonucleotide or small interfering RNA (siRNA). * Prior non-hepatitis B treatment with an oligonucleotide or siRNA within 12 months prior to the first dosing day. * Fridericia's QT correction formula (QTcF) \>=450 millisecond (msec) (if single electrocardiogram \[ECG\] at screening shows QTcF \>=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion). * History of/sensitivity to bepirovirsen, DAP/TOM or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation * Participants who do not wish to discontinue taking NA therapy for their chronic HBV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants achieving functional cure | Up to 100 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants achieving functional cure with high Baseline HBsAg level | Up to 100 Weeks | 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. |
| Number of participants achieving functional cure with low Baseline HBsAg level | Up to 100 Weeks | 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. |
| Number of participants achieving functional cure with low Baseline HBsAg level compared against placebo + bepirovirsen arm | Up to 100 Weeks | 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. |
| Number of participants with undetected HBsAg and HBV DNA <LLOQ | Up to 48 Weeks | The number of participants with undetected HBsAg and HBV DNA \<LLOQ at the end of bepirovirsen treatment will be reported. |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, Italy, Japan, New Zealand, Singapore, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed