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

Last updated: December 4, 2024
Sponsor: GlaxoSmithKline
Overall Status: Active - Recruiting

Phase

2

Condition

Hepatitis B

Liver Disorders

Hepatitis

Treatment

Bepirovirsen

Placebo

Daplusiran/Tomligisiran Dose Level 1

Clinical Study ID

NCT06537414
218309
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 currentlyreceiving stable NA therapy defined as receiving an NA regimen form at least 6months prior to Screening and with no planned changes to their stable regimen overthe 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 asplasma 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 withthe protocol.

  • Male and Female

Exclusion

Exclusion Criteria:

  • Clinically significant abnormalities, aside from chronic HBV infection in medicalhistory (e.g., moderate-severe liver disease other than chronic HBV, acute coronarysyndrome within 6 months of screening, major surgery within 3 months of screening,significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesiscoagulopathy) or clinically significant physical examination findings.

  • Coinfection with Hepatitis C (cured <12 months at the time of screening), Humanimmunodeficiency 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 cancersthat are cured by surgical resection (example, skin cancer). Participants underevaluation 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 withoutidentified cause), current or history of an autoimmune condition or history/presenceof 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) ortopical/inhaled steroid use.

  • Participants, to whom immunosuppressive treatment (including therapeutic doses ofsteroids) is contraindicated, should not be considered for enrollment in the study.

  • Currently taking, or has taken within 6 months of Screening, anyinterferon-containing therapy.

  • Participants requiring anti-coagulation therapies (example, warfarin, Factor Xainhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatmentcan 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 oligonucleotideor small interfering ribonucleic acid (RNA) (siRNA).

  • Prior non-hepatitis B treatment with an oligonucleotide or siRNA within 12 monthsprior to the first dosing day.

  • Fridericia's QT correction formula (QTcF) >=450 millisecond (msec) (if singleelectrocardiogram [ECG] at screening shows QTcF >=450 msec, a mean of triplicatemeasurements should be used to confirm that participant meets exclusion criterion).

  • History of/sensitivity to bepirovirsen, DAP/TOM or components thereof or a historyof drug or other allergy that, in the opinion of the investigator or MedicalMonitor, contraindicates their participation

  • Participants who do not wish to discontinue taking NA therapy for their chronic HBVinfection.

Study Design

Total Participants: 280
Treatment Group(s): 4
Primary Treatment: Bepirovirsen
Phase: 2
Study Start date:
November 11, 2024
Estimated Completion Date:
October 29, 2027

Connect with a study center

  • GSK Investigational Site

    Camperdown, New South Wales 2050
    Australia

    Site Not Available

  • GSK Investigational Site

    Westmead, New South Wales 2145
    Australia

    Site Not Available

  • GSK Investigational Site

    Fitzroy, Victoria 3065
    Australia

    Site Not Available

  • GSK Investigational Site

    Bruxelles, 1000
    Belgium

    Site Not Available

  • GSK Investigational Site

    Edegem, 2650
    Belgium

    Site Not Available

  • GSK Investigational Site

    Gent, 9000
    Belgium

    Site Not Available

  • GSK Investigational Site

    Aracaju, 49060-010
    Brazil

    Site Not Available

  • GSK Investigational Site

    Curitiba, 80810-050
    Brazil

    Site Not Available

  • GSK Investigational Site

    Manaus, 69040-000
    Brazil

    Site Not Available

  • GSK Investigational Site

    Sao Paulo, 05403-000
    Brazil

    Site Not Available

  • GSK Investigational Site

    Calgary, Alberta T2N 4Z6
    Canada

    Site Not Available

  • GSK Investigational Site

    Ottawa, Ontario K1H8L6
    Canada

    Site Not Available

  • GSK Investigational Site

    Toronto, Ontario L4L 4Y7
    Canada

    Site Not Available

  • GSK Investigational Site

    Montreal, Quebec H4A 3J1
    Canada

    Site Not Available

  • GSK Investigational Site

    Beijing, 100050
    China

    Site Not Available

  • GSK Investigational Site

    Chengdu, 610072
    China

    Site Not Available

  • GSK Investigational Site

    Guangzhou, 510630
    China

    Site Not Available

  • GSK Investigational Site

    Shanghai, 200040
    China

    Site Not Available

  • GSK Investigational Site

    Zhenjiang,
    China

    Site Not Available

  • GSK Investigational Site

    Clichy Cedex, 92118
    France

    Site Not Available

  • GSK Investigational Site

    CrEteil cedex, 94010
    France

    Site Not Available

  • GSK Investigational Site

    Limoges cedex, 87042
    France

    Site Not Available

  • GSK Investigational Site

    Lyon, 69004
    France

    Site Not Available

  • GSK Investigational Site

    Marseille, 13008
    France

    Site Not Available

  • GSK Investigational Site

    Toulouse Cedex 9, 31059
    France

    Site Not Available

  • GSK Investigational Site

    Berlin, 10787
    Germany

    Site Not Available

  • GSK Investigational Site

    Essen, 45122
    Germany

    Site Not Available

  • GSK Investigational Site

    Hannover, 30625
    Germany

    Site Not Available

  • GSK Investigational Site

    Leipzig, 04103
    Germany

    Site Not Available

  • GSK Investigational Site

    Muenster, 48149
    Germany

    Site Not Available

  • GSK Investigational Site

    Athens, 11527
    Greece

    Site Not Available

  • GSK Investigational Site

    Pokfulam,
    Hong Kong

    Site Not Available

  • GSK Investigational Site

    Shatin,
    Hong Kong

    Site Not Available

  • GSK Investigational Site

    Bergamo, 24127
    Italy

    Site Not Available

  • GSK Investigational Site

    Firenze, 50134
    Italy

    Site Not Available

  • GSK Investigational Site

    Milano,
    Italy

    Site Not Available

  • GSK Investigational Site

    Modena, 41126
    Italy

    Site Not Available

  • GSK Investigational Site

    Napoli, 80131
    Italy

    Site Not Available

  • GSK Investigational Site

    Padova, 35131
    Italy

    Site Not Available

  • GSK Investigational Site

    Pisa, 56124
    Italy

    Site Not Available

  • GSK Investigational Site

    Roma, 00161
    Italy

    Site Not Available

  • GSK Investigational Site

    Torino, 10126
    Italy

    Site Not Available

  • GSK Investigational Site

    Chiba, 270-1694
    Japan

    Site Not Available

  • GSK Investigational Site

    Hokkaido, 006-8555
    Japan

    Site Not Available

  • GSK Investigational Site

    Hyogo, 660-8550
    Japan

    Site Not Available

  • GSK Investigational Site

    Kagawa, 761-0793
    Japan

    Site Not Available

  • GSK Investigational Site

    Kumamoto, 860-8556
    Japan

    Site Not Available

  • GSK Investigational Site

    Osaka, 540-0006
    Japan

    Site Not Available

  • GSK Investigational Site

    Tokyo, 180-8610
    Japan

    Site Not Available

  • GSK Investigational Site

    Yamanashi, 409-3898
    Japan

    Site Not Available

  • GSK Investigational Site

    Ansan, 15355
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Busan, 47392
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Pusan, 49241
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Seoul, 138-736
    Korea, Republic of

    Site Not Available

  • GSK Investigational Site

    Auckland, 1023
    New Zealand

    Site Not Available

  • GSK Investigational Site

    Papatoetoe Auckland, 2025
    New Zealand

    Site Not Available

  • GSK Investigational Site

    Singapore, 169608
    Singapore

    Site Not Available

  • GSK Investigational Site

    Johannesburg, 2193
    South Africa

    Site Not Available

  • GSK Investigational Site

    Reiger Park, 1459
    South Africa

    Site Not Available

  • GSK Investigational Site

    Soweto Johannesburg, 2013
    South Africa

    Site Not Available

  • GSK Investigational Site

    Barcelona, 08035
    Spain

    Site Not Available

  • GSK Investigational Site

    Leon, 24080
    Spain

    Site Not Available

  • GSK Investigational Site

    Madrid, 28041
    Spain

    Site Not Available

  • GSK Investigational Site

    Salamanca, 37007
    Spain

    Site Not Available

  • GSK Investigational Site

    Santander, 39008
    Spain

    Site Not Available

  • GSK Investigational Site

    Valencia, 46026
    Spain

    Site Not Available

  • GSK Investigational Site

    Kaohsiung, 824
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Kaohsiung City, 807
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Taichung, 404
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Tau-Yuan, 333
    Taiwan

    Site Not Available

  • GSK Investigational Site

    London, SE5 9RS
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    Middlesbrough, TS4 3BW
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    San Francisco, California 94115
    United States

    Active - Recruiting

  • GSK Investigational Site

    San Jose, California 95128
    United States

    Site Not Available

  • GSK Investigational Site

    Minneapolis, Minnesota 55415
    United States

    Site Not Available

  • GSK Investigational Site

    New York, New York 10029
    United States

    Site Not Available

  • GSK Investigational Site

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

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