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Sequential therapy for chronic hepatitis B using Daplusiran/Tomligisiran and Bepirovirsen

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)

Phase 2 Interventional GlaxoSmithKline · NCT06537414

This study is testing if a new combination of two treatments can improve the care of people with chronic hepatitis B who are already on standard medication.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment280 (estimated)
Ages18 Years and up
SexAll
SponsorGlaxoSmithKline Industry-sponsored
Drugs / interventionsprednisone
Locations83 sites (San Francisco, California and 82 other locations)
Trial IDNCT06537414 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of two different doses of Daplusiran/Tomligisiran followed by Bepirovirsen in participants with chronic hepatitis B who are on standard nucleos(t)ide analogue therapy. The goal is to identify the optimal dose of DAP/TOM for sequential therapy and assess its contribution to the overall treatment regimen. Participants will be monitored for their response to the treatment and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with documented chronic HBV infection who are currently stable on nucleos(t)ide analogue therapy.

Not a fit: Patients with significant liver disease other than chronic HBV or those with recent acute coronary syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients living with chronic hepatitis B.

How similar studies have performed: Other studies have shown promise with similar sequential therapy approaches, indicating potential for success in this area.

Eligibility criteria

Show full inclusion / 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.

Where this trial is running

San Francisco, California and 82 other locations

+33 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Chronic Hepatitis B Virus InfectionHepatitis BBepirovirsenB-UNITEDDaplusiran/TomligisiranNucleoside analogue
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.