Исследование последовательной терапии даплюсираном/томлигисираном (ДАП/ТОМ) с последующим применением бепировирсена у участников, живущих с хроническим гепатитом В (ХГВ) (B-UNITED)
Фаза 2b, многоцентровое, рандомизированное, частично плацебо-контролируемое, двойное слепое исследование по изучению безопасности и эффективности последовательной терапии даплюсираном/томлигизираном с последующим применением бепировирсена у участников с хроническим вирусом гепатита В на фоне аналога нуклео(т)ид. Терапия (Б-Юнайтед)
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.
Обзор исследования
Статус
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 2
Контакты и местонахождение
Места учебы
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New South Wales
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Westmead, New South Wales, Австралия, 2145
- GSK Investigational Site
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Victoria
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Fitzroy, Victoria, Австралия, 3065
- GSK Investigational Site
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Brussels, Бельгия, 1000
- GSK Investigational Site
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Edegem, Бельгия, 2650
- GSK Investigational Site
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Oost-Vlaanderen
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Ghent, Oost-Vlaanderen, Бельгия, 9000
- GSK Investigational Site
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Aracaju, Бразилия, 49060-010
- GSK Investigational Site
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Curitiba, Бразилия, 80810-050
- GSK Investigational Site
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Manaus, Бразилия, 69040-000
- GSK Investigational Site
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São Paulo, Бразилия, 05403-000
- GSK Investigational Site
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Berlin, Германия, 10787
- GSK Investigational Site
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Berlin, Германия, 10439
- GSK Investigational Site
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Münster, Германия, 48149
- GSK Investigational Site
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Lower Saxony
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Hanover, Lower Saxony, Германия, 30625
- GSK Investigational Site
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Pokfulam, Гонконг
- GSK Investigational Site
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Shatin, Гонконг
- GSK Investigational Site
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Athens, Греция, 10676
- GSK Investigational Site
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Athens, Греция, 11527
- GSK Investigational Site
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Barcelona, Испания, 08036
- GSK Investigational Site
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Barcelona, Испания, 08035
- GSK Investigational Site
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León, Испания, 24080
- GSK Investigational Site
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Madrid, Испания, 28041
- GSK Investigational Site
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Salamanca, Испания, 37007
- GSK Investigational Site
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Santander, Испания, 39008
- GSK Investigational Site
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Valencia, Испания, 46026
- GSK Investigational Site
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Bergamo, Италия, 24127
- GSK Investigational Site
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Florence, Италия, 50134
- GSK Investigational Site
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Milan, Италия
- GSK Investigational Site
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Naples, Италия, 80131
- GSK Investigational Site
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Padova, Италия, 35131
- GSK Investigational Site
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Pisa, Италия, 56124
- GSK Investigational Site
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Roma, Италия, 00161
- GSK Investigational Site
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Alberta
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Calgary, Alberta, Канада, T2N 4Z6
- GSK Investigational Site
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Ontario
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Ottawa, Ontario, Канада, K1H8L6
- GSK Investigational Site
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Toronto, Ontario, Канада, M5G 2C4
- GSK Investigational Site
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Quebec
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Montreal, Quebec, Канада, H4A 3J1
- GSK Investigational Site
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Beijing, Китай, 100050
- GSK Investigational Site
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Chengdu, Китай, 610072
- GSK Investigational Site
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Guangzhou, Китай, 510630
- GSK Investigational Site
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Shanghai, Китай, 200040
- GSK Investigational Site
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Auckland, Новая Зеландия, 2025
- GSK Investigational Site
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Auckland, Новая Зеландия, 1023
- GSK Investigational Site
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Singapore, Сингапур, 119074
- GSK Investigational Site
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Singapore, Сингапур, 169608
- GSK Investigational Site
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London, Соединенное Королевство, SE5 9RS
- GSK Investigational Site
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London, Соединенное Королевство, SW17 0QT
- GSK Investigational Site
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London, Соединенное Королевство, E1 8PR
- GSK Investigational Site
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Middlesbrough, Соединенное Королевство, TS4 3BW
- GSK Investigational Site
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California
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San Francisco, California, Соединенные Штаты, 94115
- GSK Investigational Site
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San Jose, California, Соединенные Штаты, 95116
- GSK Investigational Site
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Minnesota
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Minneapolis, Minnesota, Соединенные Штаты, 55415
- GSK Investigational Site
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New York
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New York, New York, Соединенные Штаты, 10029
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, Соединенные Штаты, 19104
- GSK Investigational Site
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Kaohsiung City, Тайвань, 807
- GSK Investigational Site
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Kaohsiung City, Тайвань, 824
- GSK Investigational Site
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Taichung, Тайвань, 404
- GSK Investigational Site
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Tau-Yuan, Тайвань, 333
- GSK Investigational Site
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Clichy, Франция, 92118
- GSK Investigational Site
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Créteil, Франция, 94010
- GSK Investigational Site
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Limoges, Франция, 87042
- GSK Investigational Site
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Lyon, Франция, 69004
- GSK Investigational Site
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Marseille, Франция, 13008
- GSK Investigational Site
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Ekurhuleni, Южная Африка, 1459
- GSK Investigational Site
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Johannesburg, Южная Африка, 2193
- GSK Investigational Site
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Ansan, Южная Корея, 15355
- GSK Investigational Site
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Busan, Южная Корея, 47392
- GSK Investigational Site
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Pusan, Южная Корея, 49241
- GSK Investigational Site
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Seoul, Южная Корея, 138-736
- GSK Investigational Site
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Seoul, Южная Корея, 07061
- GSK Investigational Site
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Chiba, Япония, 270-1694
- GSK Investigational Site
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Hokkaido, Япония, 006-8555
- GSK Investigational Site
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Hokkaido, Япония, 053-8506
- GSK Investigational Site
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Hyōgo, Япония, 660-8550
- GSK Investigational Site
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Kagawa, Япония, 761-0793
- GSK Investigational Site
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Kagawa, Япония, 760-8557
- GSK Investigational Site
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Kumamoto, Япония, 860-8556
- GSK Investigational Site
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Kumamoto, Япония, 862-8655
- GSK Investigational Site
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Osaka, Япония, 540-0006
- GSK Investigational Site
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Osaka, Япония, 565-0871
- GSK Investigational Site
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Tokyo, Япония, 180-8610
- GSK Investigational Site
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Yamanashi, Япония, 409-3898
- GSK Investigational Site
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- 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
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 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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Последовательное назначение
- Маскировка: Двойной
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: Treatment Arm 1A: DAP/TOM + Bepirovirsen
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. |
Daplusiran/Tomligisiran dose level 1 will be administered Bepirovirsen will be administered |
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Экспериментальный: Treatment Arm 1B: DAP/TOM + Bepirovirsen
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. |
Bepirovirsen will be administered Daplusiran/Tomligisiran dose level 2 will be administered |
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Экспериментальный: Treatment Arm 2A: DAP/TOM + Bepirovirsen
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. |
Daplusiran/Tomligisiran dose level 1 will be administered Bepirovirsen will be administered |
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Экспериментальный: Treatment Arm 2B: DAP/TOM + Bepirovirsen
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. |
Bepirovirsen will be administered Daplusiran/Tomligisiran dose level 2 will be administered |
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Экспериментальный: Treatment Arm 2C: Placebo + Bepirovirsen
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. |
Placebo will be administered Bepirovirsen will be administered |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Number of participants achieving functional cure
Временное ограничение: Up to 100 Weeks
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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. |
Up to 100 Weeks
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Number of participants achieving functional cure with high Baseline HBsAg level
Временное ограничение: Up to 100 Weeks
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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. |
Up to 100 Weeks
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Number of participants achieving functional cure with low Baseline HBsAg level
Временное ограничение: Up to 100 Weeks
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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. |
Up to 100 Weeks
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Number of participants achieving functional cure with low Baseline HBsAg level compared against placebo + bepirovirsen arm
Временное ограничение: Up to 100 Weeks
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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. |
Up to 100 Weeks
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Number of participants with undetected HBsAg and HBV DNA <LLOQ
Временное ограничение: Up to 48 Weeks
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The number of participants with undetected HBsAg and HBV DNA <LLOQ at the end of bepirovirsen treatment will be reported. |
Up to 48 Weeks
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Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: GSK Clinical Trials, GlaxoSmithKline
Публикации и полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Инфекции, передающиеся через кровь
- Патологические процессы
- Хроническое заболевание
- Атрибуты болезни
- Инфекции
- Вирусные заболевания
- Заболевания пищеварительной системы
- Заболевания печени
- Гепатит, Вирусный, Человеческий
- Передающиеся заболевания
- ДНК-вирусные инфекции
- Гепаднавирусные инфекции
- Гепатит, хронический
- Гепатит
- Патологические состояния, признаки и симптомы
- Гепатит Б
- Гепатит В, хронический
Другие идентификационные номера исследования
- 218309
- 2024-514507-33-00 (Ктис)
- 2024-514507-33-00 (Идентификатор реестра: CTIS (EU))
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Описание плана IPD
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
Сроки обмена IPD
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.
Критерии совместного доступа к IPD
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.
Совместное использование IPD Поддерживающий тип информации
- STUDY_PROTOCOL
- САП
- МКФ
- КСО
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .