Last updated: 07/25/2025 11:20:09
A study of sequential therapy with daplusiran/tomligisiran (DAP/TOM) followed by bepirovirsen in participants living with chronic hepatitis B (CHB)B-UNITED
GSK study ID
218309
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Active, not recruiting
Active, not recruiting
Trial overview
Official title: A Phase 2b, multi-centre, randomized, partially placebo-controlled, double-blind study to investigate the safety and efficacy of sequential therapy with daplusiran/tomligisiran followed by bepirovirsen in participants with chronic hepatitis B virus on background nucleos(t)ide analogue therapy (B-United)
Trial description: 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 purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants achieving functional cure
Timeframe: Up to 100 Weeks
Secondary outcomes:
Number of participants achieving functional cure with high Baseline HBsAg level
Timeframe: Up to 100 Weeks
Number of participants achieving functional cure with low Baseline HBsAg level
Timeframe: Up to 100 Weeks
Number of participants achieving functional cure with low Baseline HBsAg level compared against placebo + bepirovirsen arm
Timeframe: Up to 100 Weeks
Number of participants with undetected HBsAg and HBV DNA <LLOQ
Timeframe: Up to 48 Weeks
Interventions:
Drug: Daplusiran/Tomligisiran Dose Level 1
Drug: Daplusiran/Tomligisiran Dose Level 2
Drug: Bepirovirsen
Drug: Placebo
Enrollment:
283
Observational study model:
Not applicable
Primary completion date:
2027-31-05
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Chronic Hepatitis B virus infection, Hepatitis B
Product
Bepirovirsen+Daplusiran+Tomligisiran
Collaborators
Not applicable
Study date(s)
November 2024 to May 2027
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Age: At least 18 years of age at the time of signing the informed consent.
- Documented chronic HBV infection >=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.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- Age: At least 18 years of age at the time of signing the informed consent.
- Documented chronic HBV infection >=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 >100 international units per milliliter (IU/mL)
- Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
- Alanine aminotransferase <=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 ribonucleic acid (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.
Trial location(s)
Location
GSK Investigational Site
Philadelphia, PA, United States, 19104
Status
Recruitment Complete
Location
GSK Investigational Site
San Francisco, CA, United States, 94115
Status
Recruitment Complete
Location
GSK Investigational Site
San Jose, CA, United States, 95128
Status
Recruitment Complete
Location
GSK Investigational Site
Papatoetoe Auckland, New Zealand, 2025
Status
Recruitment Complete
Location
GSK Investigational Site
Minneapolis, MN, United States, 55415
Status
Recruitment Complete
Location
GSK Investigational Site
Soweto Johannesburg, South Africa, 2013
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Johannesburg, South Africa, 2193
Status
Recruitment Complete
Location
GSK Investigational Site
London, United Kingdom, SW17 0QT
Status
Recruitment Complete
Location
GSK Investigational Site
Middlesbrough, United Kingdom, TS4 3BW
Status
Recruitment Complete
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Active, not recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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