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

NCT06537414 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 218309
• Study Type: interventional
• Target: 283
• Locations: 19 countries
• Sites: 81

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.

Conditions

Chronic Hepatitis B Virus Infection; Hepatitis B

Keywords

Bepirovirsen; B-UNITED; Daplusiran/Tomligisiran; Hepatitis B; Nucleos(t)ide analogue

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of participants achieving functional cure with high Baseline HBsAg level

  Up to 100 Weeks

• Number of participants achieving functional cure with low Baseline HBsAg level

  Up to 100 Weeks

• Number of participants achieving functional cure with low Baseline HBsAg level compared against placebo + bepirovirsen arm

  Up to 100 Weeks

• Number of participants with undetected HBsAg and HBV DNA <LLOQ

  Up to 48 Weeks

Study Arms (5)

Treatment Arm 1A: DAP/TOM + Bepirovirsen

EXPERIMENTAL

Participants 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.

Drug: Daplusiran/Tomligisiran Dose Level 1; Drug: Bepirovirsen

Treatment Arm 1B: DAP/TOM + Bepirovirsen

EXPERIMENTAL

Participants 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.

Drug: Daplusiran/Tomligisiran Dose Level 2; Drug: Bepirovirsen

Treatment Arm 2A: DAP/TOM + Bepirovirsen

EXPERIMENTAL

Participants 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.

Drug: Daplusiran/Tomligisiran Dose Level 1; Drug: Bepirovirsen

Treatment Arm 2B: DAP/TOM + Bepirovirsen

EXPERIMENTAL

Participants 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.

Drug: Daplusiran/Tomligisiran Dose Level 2; Drug: Bepirovirsen

Treatment Arm 2C: Placebo + Bepirovirsen

EXPERIMENTAL

Participants 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.

Drug: Bepirovirsen; Drug: Placebo

Interventions

Daplusiran/Tomligisiran Dose Level 1 DRUG

Daplusiran/Tomligisiran dose level 1 will be administered

Treatment Arm 1A: DAP/TOM + Bepirovirsen; Treatment Arm 2A: DAP/TOM + Bepirovirsen

Daplusiran/Tomligisiran Dose Level 2 DRUG

Daplusiran/Tomligisiran dose level 2 will be administered

Treatment Arm 1B: DAP/TOM + Bepirovirsen; Treatment Arm 2B: DAP/TOM + Bepirovirsen

Bepirovirsen DRUG

Bepirovirsen will be administered

Treatment Arm 1A: DAP/TOM + Bepirovirsen; Treatment Arm 1B: DAP/TOM + Bepirovirsen; Treatment Arm 2A: DAP/TOM + Bepirovirsen; Treatment Arm 2B: DAP/TOM + Bepirovirsen; Treatment Arm 2C: Placebo + Bepirovirsen

Placebo DRUG

Placebo will be administered

Treatment Arm 2C: Placebo + Bepirovirsen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (81)

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

San Jose, California, 95128, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55415, United States

Location

GSK Investigational Site

New York, New York, 10029, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Westmead, New South Wales, 2145, Australia

Location

GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Aracaju, 49060-010, Brazil

Location

GSK Investigational Site

Curitiba, 80810-050, Brazil

Location

GSK Investigational Site

Manaus, 69040-000, Brazil

Location

GSK Investigational Site

São Paulo, 05403-000, Brazil

Location

GSK Investigational Site

Calgary, Alberta, T2N 4Z6, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1H8L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2C4, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Beijing, 100050, China

Location

GSK Investigational Site

Chengdu, 610072, China

Location

GSK Investigational Site

Guangzhou, 510630, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Clichy, 92118, France

Location

GSK Investigational Site

Créteil, 94010, France

Location

GSK Investigational Site

Limoges, 87042, France

Location

GSK Investigational Site

Lyon, 69004, France

Location

GSK Investigational Site

Marseille, 13008, France

Location

GSK Investigational Site

Toulouse, 31059, France

Location

GSK Investigational Site

Berlin, 10439, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Hanover, 30625, Germany

Location

GSK Investigational Site

Münster, 48149, Germany

Location

GSK Investigational Site

Athens, 10676, Greece

Location

GSK Investigational Site

Athens, 11527, Greece

Location

GSK Investigational Site

Pokfulam, Hong Kong

Location

GSK Investigational Site

Shatin, Hong Kong

Location

GSK Investigational Site

Bergamo, 24127, Italy

Location

GSK Investigational Site

Florence, 50134, Italy

Location

GSK Investigational Site

Milan, Italy

Location

GSK Investigational Site

Napoli, 80131, Italy

Location

GSK Investigational Site

Padua, 35131, Italy

Location

GSK Investigational Site

Pisa, 56124, Italy

Location

GSK Investigational Site

Roma, 00161, Italy

Location

GSK Investigational Site

Chiba, 270-1694, Japan

Location

GSK Investigational Site

Hokkaido, 006-8555, Japan

Location

GSK Investigational Site

Hokkaido, 053-8506, Japan

Location

GSK Investigational Site

Hyōgo, 660-8550, Japan

Location

GSK Investigational Site

Kagawa, 760-8557, Japan

Location

GSK Investigational Site

Kagawa, 761-0793, Japan

Location

GSK Investigational Site

Kumamoto, 860-8556, Japan

Location

GSK Investigational Site

Kumamoto, 862-8655, Japan

Location

GSK Investigational Site

Osaka, 540-0006, Japan

Location

GSK Investigational Site

Osaka, 565-0871, Japan

Location

GSK Investigational Site

Tokyo, 180-8610, Japan

Location

GSK Investigational Site

Yamanashi, 409-3898, Japan

Location

GSK Investigational Site

Auckland, 1023, New Zealand

Location

GSK Investigational Site

Papatoetoe Auckland, 2025, New Zealand

Location

GSK Investigational Site

Singapore, 119074, Singapore

Location

GSK Investigational Site

Singapore, 169608, Singapore

Location

GSK Investigational Site

Johannesburg, 2193, South Africa

Location

GSK Investigational Site

Reiger Park, 1459, South Africa

Location

GSK Investigational Site

Ansan, 15355, South Korea

Location

GSK Investigational Site

Busan, 47392, South Korea

Location

GSK Investigational Site

Pusan, 49241, South Korea

Location

GSK Investigational Site

Seoul, 07061, South Korea

Location

GSK Investigational Site

Seoul, 138-736, South Korea

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

León, 24080, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Salamanca, 37007, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Kaohsiung City, 807, Taiwan

Location

GSK Investigational Site

Kaohsiung City, 824, Taiwan

Location

GSK Investigational Site

Taichung, 404, Taiwan

Location

GSK Investigational Site

Tau-Yuan, 333, Taiwan

Location

GSK Investigational Site

London, E1 8PR, United Kingdom

Location

GSK Investigational Site

London, SE5 9RS, United Kingdom

Location

GSK Investigational Site

London, SW17 0QT, United Kingdom

Location

GSK Investigational Site

Middlesbrough, TS4 3BW, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 5, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

GR (2); DE (4); BR (4); CN (4); KR (5); SG (2); US (5); JP (12); GB (4); ZA (2); BE (3); HK (2); IT (7); NZ (2); ES (7); TW (4); FR (6); CA (4); AU (2)