Studie sekvenční terapie Daplusiran/Tomligisiran (DAP/TOM) následovaná Bepirovirsenem u účastníků žijících s chronickou hepatitidou B (CHB) (B-UNITED)
Fáze 2b, multicentrická, randomizovaná, částečně placebem kontrolovaná, dvojitě zaslepená studie k prozkoumání bezpečnosti a účinnosti sekvenční terapie daplusiran/Tomligisiran následovaná Bepirovirsenem u účastníků s chronickým virem hepatitidy B na pozadí analog Nucleos(t)Ide Terapie (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.
Přehled studie
Postavení
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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New South Wales
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Westmead, New South Wales, Austrálie, 2145
- GSK Investigational Site
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Victoria
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Fitzroy, Victoria, Austrálie, 3065
- GSK Investigational Site
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Brussels, Belgie, 1000
- GSK Investigational Site
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Edegem, Belgie, 2650
- GSK Investigational Site
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Oost-Vlaanderen
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Ghent, Oost-Vlaanderen, Belgie, 9000
- GSK Investigational Site
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Aracaju, Brazílie, 49060-010
- GSK Investigational Site
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Curitiba, Brazílie, 80810-050
- GSK Investigational Site
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Manaus, Brazílie, 69040-000
- GSK Investigational Site
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São Paulo, Brazílie, 05403-000
- GSK Investigational Site
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Clichy, Francie, 92118
- GSK Investigational Site
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Créteil, Francie, 94010
- GSK Investigational Site
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Limoges, Francie, 87042
- GSK Investigational Site
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Lyon, Francie, 69004
- GSK Investigational Site
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Marseille, Francie, 13008
- GSK Investigational Site
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Pokfulam, Hongkong
- GSK Investigational Site
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Shatin, Hongkong
- GSK Investigational Site
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Bergamo, Itálie, 24127
- GSK Investigational Site
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Florence, Itálie, 50134
- GSK Investigational Site
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Milan, Itálie
- GSK Investigational Site
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Naples, Itálie, 80131
- GSK Investigational Site
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Padova, Itálie, 35131
- GSK Investigational Site
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Pisa, Itálie, 56124
- GSK Investigational Site
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Roma, Itálie, 00161
- GSK Investigational Site
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Chiba, Japonsko, 270-1694
- GSK Investigational Site
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Hokkaido, Japonsko, 006-8555
- GSK Investigational Site
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Hokkaido, Japonsko, 053-8506
- GSK Investigational Site
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Hyōgo, Japonsko, 660-8550
- GSK Investigational Site
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Kagawa, Japonsko, 761-0793
- GSK Investigational Site
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Kagawa, Japonsko, 760-8557
- GSK Investigational Site
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Kumamoto, Japonsko, 860-8556
- GSK Investigational Site
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Kumamoto, Japonsko, 862-8655
- GSK Investigational Site
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Osaka, Japonsko, 540-0006
- GSK Investigational Site
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Osaka, Japonsko, 565-0871
- GSK Investigational Site
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Tokyo, Japonsko, 180-8610
- GSK Investigational Site
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Yamanashi, Japonsko, 409-3898
- GSK Investigational Site
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Ekurhuleni, Jižní Afrika, 1459
- GSK Investigational Site
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Johannesburg, Jižní Afrika, 2193
- GSK Investigational Site
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Ansan, Jižní Korea, 15355
- GSK Investigational Site
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Busan, Jižní Korea, 47392
- GSK Investigational Site
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Pusan, Jižní Korea, 49241
- GSK Investigational Site
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Seoul, Jižní Korea, 138-736
- GSK Investigational Site
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Seoul, Jižní Korea, 07061
- GSK Investigational Site
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Alberta
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Calgary, Alberta, Kanada, T2N 4Z6
- GSK Investigational Site
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Ontario
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Ottawa, Ontario, Kanada, K1H8L6
- GSK Investigational Site
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Toronto, Ontario, Kanada, M5G 2C4
- GSK Investigational Site
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Quebec
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Montreal, Quebec, Kanada, H4A 3J1
- GSK Investigational Site
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Auckland, Nový Zéland, 2025
- GSK Investigational Site
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Auckland, Nový Zéland, 1023
- GSK Investigational Site
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Berlin, Německo, 10787
- GSK Investigational Site
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Berlin, Německo, 10439
- GSK Investigational Site
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Münster, Německo, 48149
- GSK Investigational Site
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Lower Saxony
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Hanover, Lower Saxony, Německo, 30625
- GSK Investigational Site
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Singapore, Singapur, 119074
- GSK Investigational Site
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Singapore, Singapur, 169608
- GSK Investigational Site
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London, Spojené království, SE5 9RS
- GSK Investigational Site
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London, Spojené království, SW17 0QT
- GSK Investigational Site
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London, Spojené království, E1 8PR
- GSK Investigational Site
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Middlesbrough, Spojené království, TS4 3BW
- GSK Investigational Site
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California
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San Francisco, California, Spojené státy, 94115
- GSK Investigational Site
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San Jose, California, Spojené státy, 95116
- GSK Investigational Site
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Minnesota
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Minneapolis, Minnesota, Spojené státy, 55415
- GSK Investigational Site
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New York
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New York, New York, Spojené státy, 10029
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19104
- GSK Investigational Site
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Kaohsiung City, Tchaj-wan, 807
- GSK Investigational Site
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Kaohsiung City, Tchaj-wan, 824
- GSK Investigational Site
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Taichung, Tchaj-wan, 404
- GSK Investigational Site
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Tau-Yuan, Tchaj-wan, 333
- GSK Investigational Site
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Beijing, Čína, 100050
- GSK Investigational Site
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Chengdu, Čína, 610072
- GSK Investigational Site
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Guangzhou, Čína, 510630
- GSK Investigational Site
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Shanghai, Čína, 200040
- GSK Investigational Site
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Athens, Řecko, 10676
- GSK Investigational Site
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Athens, Řecko, 11527
- GSK Investigational Site
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Barcelona, Španělsko, 08036
- GSK Investigational Site
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Barcelona, Španělsko, 08035
- GSK Investigational Site
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León, Španělsko, 24080
- GSK Investigational Site
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Madrid, Španělsko, 28041
- GSK Investigational Site
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Salamanca, Španělsko, 37007
- GSK Investigational Site
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Santander, Španělsko, 39008
- GSK Investigational Site
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Valencia, Španělsko, 46026
- GSK Investigational Site
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: 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 |
|
Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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 |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Number of participants achieving functional cure
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Number of participants achieving functional cure with high Baseline HBsAg level
Časové okno: 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
Časové okno: 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
Časové okno: Up to 100 Weeks
|
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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: GSK Clinical Trials, GlaxoSmithKline
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Infekce přenášené krví
- Patologické procesy
- Chronické onemocnění
- Atributy nemoci
- Infekce
- Virová onemocnění
- Nemoci trávicího systému
- Onemocnění jater
- Hepatitida, virová, lidská
- Přenosné nemoci
- DNA virové infekce
- Infekce Hepadnaviridae
- Hepatitida, chronická
- Hepatitida
- Patologické stavy, příznaky a symptomy
- Žloutenka typu B
- Hepatitida B, chronická
Další identifikační čísla studie
- 218309
- 2024-514507-33-00 (Ctis)
- 2024-514507-33-00 (Identifikátor registru: CTIS (EU))
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu 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
Časový rámec sdílení 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.
Kritéria přístupu pro sdílení 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.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
- CSR
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .