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Chronic Hepatitis B Virus InfectionPhase 2B-UNITEDNCT06537414

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

A Phase 2 study testing Daplusiran/Tomligisiran Dose Level 1, Daplusiran/Tomligisiran Dose Level 2 and Bepirovirsen in people with Chronic Hepatitis B Virus Infection and Hepatitis B, run by GlaxoSmithKline at 80 sites in 19 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Daplusiran/Tomligisiran Dose Level 1, Daplusiran/Tomligisiran Dose Level 2 and Bepirovirsen
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
283 participants
Where
80 sitesin 19 countries
Study dates
11 Nov 2024to 17 May 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

80 sites in 19 countries.

80 sites in 19 countries

Japan12 sites

  • GSK Investigational Site

    Chiba, 270-1694

  • GSK Investigational Site

    Hokkaido, 006-8555

  • GSK Investigational Site

    Hokkaido, 053-8506

  • GSK Investigational Site

    Hyōgo, 660-8550

  • GSK Investigational Site

    Kagawa, 760-8557

  • GSK Investigational Site

    Kagawa, 761-0793

  • GSK Investigational Site

    Kumamoto, 860-8556

  • GSK Investigational Site

    Kumamoto, 862-8655

  • GSK Investigational Site

    Osaka, 540-0006

  • GSK Investigational Site

    Osaka, 565-0871

  • GSK Investigational Site

    Tokyo, 180-8610

  • GSK Investigational Site

    Yamanashi, 409-3898

Other trials in Japan

Italy7 sites

  • GSK Investigational Site

    Bergamo, 24127

  • GSK Investigational Site

    Florence, 50134

  • GSK Investigational Site

    Milan

  • GSK Investigational Site

    Naples, 80131

  • GSK Investigational Site

    Padova, 35131

  • GSK Investigational Site

    Pisa, 56124

  • GSK Investigational Site

    Roma, 00161

Other trials in Italy

Spain7 sites

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    León, 24080

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Salamanca, 37007

  • GSK Investigational Site

    Santander, 39008

  • GSK Investigational Site

    Valencia, 46026

Other trials in Spain

United States5 sites

  • GSK Investigational Site

    Minneapolis, Minnesota, 55415

  • GSK Investigational Site

    New York, New York, 10029

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19104

  • GSK Investigational Site

    San Francisco, California, 94115

  • GSK Investigational Site

    San Jose, California, 95116

Other trials in United States

France5 sites

  • GSK Investigational Site

    Clichy, 92118

  • GSK Investigational Site

    Créteil, 94010

  • GSK Investigational Site

    Limoges, 87042

  • GSK Investigational Site

    Lyon, 69004

  • GSK Investigational Site

    Marseille, 13008

Other trials in France

South Korea5 sites

  • GSK Investigational Site

    Ansan, 15355

  • GSK Investigational Site

    Busan, 47392

  • GSK Investigational Site

    Pusan, 49241

  • GSK Investigational Site

    Seoul, 07061

  • GSK Investigational Site

    Seoul, 138-736

Other trials in South Korea

Brazil4 sites

  • GSK Investigational Site

    Aracaju, 49060-010

  • GSK Investigational Site

    Curitiba, 80810-050

  • GSK Investigational Site

    Manaus, 69040-000

  • GSK Investigational Site

    São Paulo, 05403-000

Other trials in Brazil

Canada4 sites

  • GSK Investigational Site

    Calgary, Alberta, T2N 4Z6

  • GSK Investigational Site

    Montreal, Quebec, H4A 3J1

  • GSK Investigational Site

    Ottawa, Ontario, K1H8L6

  • GSK Investigational Site

    Toronto, Ontario, M5G 2C4

Other trials in Canada

China4 sites

  • GSK Investigational Site

    Beijing, 100050

  • GSK Investigational Site

    Chengdu, 610072

  • GSK Investigational Site

    Guangzhou, 510630

  • GSK Investigational Site

    Shanghai, 200040

Other trials in China

Germany4 sites

  • GSK Investigational Site

    Berlin, 10439

  • GSK Investigational Site

    Berlin, 10787

  • GSK Investigational Site

    Hanover, 30625

  • GSK Investigational Site

    Münster, 48149

Other trials in Germany

Taiwan4 sites

  • GSK Investigational Site

    Kaohsiung City, 807

  • GSK Investigational Site

    Kaohsiung City, 824

  • GSK Investigational Site

    Taichung, 404

  • GSK Investigational Site

    Tau-Yuan, 333

Other trials in Taiwan

United Kingdom4 sites

  • GSK Investigational Site

    London, E1 8PR

  • GSK Investigational Site

    London, SE5 9RS

  • GSK Investigational Site

    London, SW17 0QT

  • GSK Investigational Site

    Middlesbrough, TS4 3BW

Other trials in United Kingdom

Belgium3 sites

  • GSK Investigational Site

    Brussels, 1000

  • GSK Investigational Site

    Edegem, 2650

  • GSK Investigational Site

    Ghent, 9000

Other trials in Belgium

Australia2 sites

  • GSK Investigational Site

    Fitzroy, Victoria, 3065

  • GSK Investigational Site

    Westmead, New South Wales, 2145

Other trials in Australia

Greece2 sites

  • GSK Investigational Site

    Athens, 10676

  • GSK Investigational Site

    Athens, 11527

Other trials in Greece

Hong Kong2 sites

  • GSK Investigational Site

    Pokfulam

  • GSK Investigational Site

    Shatin

Other trials in Hong Kong

New Zealand2 sites

  • GSK Investigational Site

    Auckland, 1023

  • GSK Investigational Site

    Papatoetoe Auckland, 2025

Other trials in New Zealand

Singapore2 sites

  • GSK Investigational Site

    Singapore, 119074

  • GSK Investigational Site

    Singapore, 169608

Other trials in Singapore

South Africa2 sites

  • GSK Investigational Site

    Johannesburg, 2193

  • GSK Investigational Site

    Reiger Park, 1459

Other trials in South Africa

About this study

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)

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.

Being tested
Daplusiran/Tomligisiran Dose Level 1, Daplusiran/Tomligisiran Dose Level 2, Bepirovirsen, Placebo
Keywords
Bepirovirsen, B-UNITED, Daplusiran/Tomligisiran, Hepatitis B, Nucleos(t)ide analogue
Medical subject headings
Hepatitis B, Chronic, Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Daplusiran/Tomligisiran Dose Level 1Drug

    Daplusiran/Tomligisiran dose level 1 will be administered

  • Daplusiran/Tomligisiran Dose Level 2Drug

    Daplusiran/Tomligisiran dose level 2 will be administered

  • BepirovirsenDrug

    Bepirovirsen will be administered

  • PlaceboDrug

    Placebo will be administered

Study groups in NCT06537414
Study groupRoleWhat they receive
Treatment Arm 1A: DAP/TOM + BepirovirsenExperimentalParticipants with high Hepatitis B surface antigen (HBsAg) level will receive dose level 1 of DAP/TOM in Treatment Stage 1. After DAP/TOM Treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.
Receives: Drug: Daplusiran/Tomligisiran Dose Level 1; Drug: Bepirovirsen
Treatment Arm 1B: DAP/TOM + BepirovirsenExperimentalParticipants with high HBsAg level will receive dose level 2 of DAP/TOM in Treatment Stage 1. After DAP/TOM treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.
Receives: Drug: Daplusiran/Tomligisiran Dose Level 2; Drug: Bepirovirsen
Treatment Arm 2A: DAP/TOM + BepirovirsenExperimentalParticipants with low HBsAg level will receive dose level 1 of DAP/TOM in Treatment Stage 1. After DAP/TOM treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.
Receives: Drug: Daplusiran/Tomligisiran Dose Level 1; Drug: Bepirovirsen
Treatment Arm 2B: DAP/TOM + BepirovirsenExperimentalParticipants with low HBsAg level will receive dose level 2 of DAP/TOM in Treatment Stage 1. After DAP/TOM treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.
Receives: Drug: Daplusiran/Tomligisiran Dose Level 2; Drug: Bepirovirsen
Treatment Arm 2C: Placebo + BepirovirsenExperimentalParticipants with low HBsAg level will receive Placebo in Treatment Stage 1. After Placebo treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.
Receives: Drug: Bepirovirsen; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 100 Weeks

Secondary outcomes (4)

  1. 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.

    Measured: Up to 100 Weeks

  2. 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.

    Measured: Up to 100 Weeks

  3. 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.

    Measured: Up to 100 Weeks

  4. 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.

    Measured: Up to 48 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2024
  2. Study start11 Nov 2024
  3. Primary completion31 May 2027 (estimated)
  4. Study completion17 May 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
283 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06537414
Sponsor's protocol ID
218309
Other IDs
2024-514507-33-00
Acronym
B-UNITED
Status last verified
Jul 2026
First submitted
1 Aug 2024
Last updated
7 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf

Publications

  • Hong J, Rajwanshi VK. Antisense oligonucleotides as drugs with both direct and indirect antiviral actions. Antiviral Res. 2025 Aug;240:106219. doi: 10.1016/j.antiviral.2025.106219. Epub 2025 Jun 23.

    PubMed 40562220

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daplusiran/Tomligisiran Dose Level 1, Daplusiran/Tomligisiran Dose Level 2 and Bepirovirsen in people with Chronic Hepatitis B Virus Infection and Hepatitis B, run by GlaxoSmithKline at 80 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in Japan, Italy, Spain, United States, France and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants achieving functional cure (time frame: Up to 100 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06537414, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.

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