En studie av sekvensiell terapi med Daplusiran/Tomligisiran (DAP/TOM) etterfulgt av Bepirovirsen i deltakere som lever med kronisk hepatitt B (CHB) (B-UNITED)
En fase 2b, multisenter, randomisert, delvis placebokontrollert, dobbeltblind studie for å undersøke sikkerheten og effekten av sekvensiell terapi med Daplusiran/Tomligisiran etterfulgt av Bepirovirsen hos deltakere med kronisk hepatitt B-virus på bakgrunnsnukleos(t)Ide-analog Terapi (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.
Studieoversikt
Status
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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New South Wales
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Westmead, New South Wales, Australia, 2145
- GSK Investigational Site
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Victoria
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Fitzroy, Victoria, Australia, 3065
- GSK Investigational Site
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Brussels, Belgia, 1000
- GSK Investigational Site
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Edegem, Belgia, 2650
- GSK Investigational Site
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Oost-Vlaanderen
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Ghent, Oost-Vlaanderen, Belgia, 9000
- GSK Investigational Site
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Aracaju, Brasil, 49060-010
- GSK Investigational Site
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Curitiba, Brasil, 80810-050
- GSK Investigational Site
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Manaus, Brasil, 69040-000
- GSK Investigational Site
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São Paulo, Brasil, 05403-000
- GSK Investigational Site
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Alberta
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Calgary, Alberta, Canada, T2N 4Z6
- GSK Investigational Site
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Ontario
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Ottawa, Ontario, Canada, K1H8L6
- GSK Investigational Site
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Toronto, Ontario, Canada, M5G 2C4
- GSK Investigational Site
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Quebec
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Montreal, Quebec, Canada, H4A 3J1
- GSK Investigational Site
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California
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San Francisco, California, Forente stater, 94115
- GSK Investigational Site
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San Jose, California, Forente stater, 95116
- GSK Investigational Site
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Minnesota
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Minneapolis, Minnesota, Forente stater, 55415
- GSK Investigational Site
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New York
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New York, New York, Forente stater, 10029
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- GSK Investigational Site
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Clichy, Frankrike, 92118
- GSK Investigational Site
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Créteil, Frankrike, 94010
- GSK Investigational Site
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Limoges, Frankrike, 87042
- GSK Investigational Site
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Lyon, Frankrike, 69004
- GSK Investigational Site
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Marseille, Frankrike, 13008
- GSK Investigational Site
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Athens, Hellas, 10676
- GSK Investigational Site
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Athens, Hellas, 11527
- GSK Investigational Site
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Pokfulam, Hong Kong
- GSK Investigational Site
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Shatin, Hong Kong
- GSK Investigational Site
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Bergamo, Italia, 24127
- GSK Investigational Site
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Florence, Italia, 50134
- GSK Investigational Site
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Milan, Italia
- GSK Investigational Site
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Naples, Italia, 80131
- GSK Investigational Site
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Padova, Italia, 35131
- GSK Investigational Site
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Pisa, Italia, 56124
- GSK Investigational Site
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Roma, Italia, 00161
- GSK Investigational Site
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Chiba, Japan, 270-1694
- GSK Investigational Site
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Hokkaido, Japan, 006-8555
- GSK Investigational Site
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Hokkaido, Japan, 053-8506
- GSK Investigational Site
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Hyōgo, Japan, 660-8550
- GSK Investigational Site
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Kagawa, Japan, 761-0793
- GSK Investigational Site
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Kagawa, Japan, 760-8557
- GSK Investigational Site
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Kumamoto, Japan, 860-8556
- GSK Investigational Site
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Kumamoto, Japan, 862-8655
- GSK Investigational Site
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Osaka, Japan, 540-0006
- GSK Investigational Site
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Osaka, Japan, 565-0871
- GSK Investigational Site
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Tokyo, Japan, 180-8610
- GSK Investigational Site
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Yamanashi, Japan, 409-3898
- GSK Investigational Site
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Beijing, Kina, 100050
- GSK Investigational Site
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Chengdu, Kina, 610072
- GSK Investigational Site
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Guangzhou, Kina, 510630
- GSK Investigational Site
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Shanghai, Kina, 200040
- GSK Investigational Site
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Auckland, New Zealand, 2025
- GSK Investigational Site
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Auckland, New Zealand, 1023
- GSK Investigational Site
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Singapore, Singapore, 119074
- GSK Investigational Site
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Singapore, Singapore, 169608
- GSK Investigational Site
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Barcelona, Spania, 08036
- GSK Investigational Site
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Barcelona, Spania, 08035
- GSK Investigational Site
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León, Spania, 24080
- GSK Investigational Site
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Madrid, Spania, 28041
- GSK Investigational Site
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Salamanca, Spania, 37007
- GSK Investigational Site
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Santander, Spania, 39008
- GSK Investigational Site
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Valencia, Spania, 46026
- GSK Investigational Site
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London, Storbritannia, SE5 9RS
- GSK Investigational Site
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London, Storbritannia, SW17 0QT
- GSK Investigational Site
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London, Storbritannia, E1 8PR
- GSK Investigational Site
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Middlesbrough, Storbritannia, TS4 3BW
- GSK Investigational Site
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Ansan, Sør -Korea, 15355
- GSK Investigational Site
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Busan, Sør -Korea, 47392
- GSK Investigational Site
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Pusan, Sør -Korea, 49241
- GSK Investigational Site
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Seoul, Sør -Korea, 138-736
- GSK Investigational Site
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Seoul, Sør -Korea, 07061
- GSK Investigational Site
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Ekurhuleni, Sør-Afrika, 1459
- GSK Investigational Site
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Johannesburg, Sør-Afrika, 2193
- GSK Investigational Site
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Kaohsiung City, Taiwan, 807
- GSK Investigational Site
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Kaohsiung City, Taiwan, 824
- GSK Investigational Site
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Taichung, Taiwan, 404
- GSK Investigational Site
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Tau-Yuan, Taiwan, 333
- GSK Investigational Site
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Berlin, Tyskland, 10787
- GSK Investigational Site
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Berlin, Tyskland, 10439
- GSK Investigational Site
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Münster, Tyskland, 48149
- GSK Investigational Site
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Lower Saxony
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Hanover, Lower Saxony, Tyskland, 30625
- GSK Investigational Site
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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 |
|
Eksperimentell: 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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Eksperimentell: 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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Eksperimentell: 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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Eksperimentell: 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 |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Number of participants achieving functional cure
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Number of participants achieving functional cure with high Baseline HBsAg level
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: GSK Clinical Trials, GlaxoSmithKline
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Blodbårne infeksjoner
- Patologiske prosesser
- Kronisk sykdom
- Sykdomsattributter
- Infeksjoner
- Virussykdommer
- Sykdommer i fordøyelsessystemet
- Leversykdommer
- Hepatitt, viral, menneskelig
- Smittsomme sykdommer
- DNA-virusinfeksjoner
- Hepadnaviridae-infeksjoner
- Hepatitt, kronisk
- Hepatitt
- Patologiske tilstander, tegn og symptomer
- Hepatitt B
- Hepatitt B, kronisk
Andre studie-ID-numre
- 218309
- 2024-514507-33-00 (Ctis)
- 2024-514507-33-00 (Registeridentifikator: CTIS (EU))
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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
IPD-delingstidsramme
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.
Tilgangskriterier for IPD-deling
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.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
- CSR
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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