Resumen

Este estudio tiene como objetivo confirmar la eficacia, seguridad, perfil farmacocinético (FC) y la durabilidad de la supresión del antígeno de superficie del virus de la hepatitis B (HBsAg) observada con bepirovirsen durante 24 semanas (con dosis de carga) en comparación con el brazo de placebo. El estudio tendrá 4 etapas: a) Tratamiento doble ciego (bepirovirsen o placebo) durante 24 semanas. b) Tratamiento con análogo de nucleós(t)ido (NA) durante 24 semanas. c) Etapa de cese del NA O continuación del NA durante 24 semanas. d) Durabilidad de la respuesta y seguimiento durante 24 semanas adicionales para los participantes que interrumpieron el tratamiento con NA en la Semana 48. Los brazos serán estratificados según el nivel de HBsAg (HBsAg mayor o igual a [≥] 100 unidades internacionales por mililitro [UI/mL] hasta menor o igual [≤] 1000 UI/mL o mayor [>] 1000 UI/mL hasta ≤ 3000 UI/mL) en el momento del tamizaje. La duración total del estudio, incluido el tamizaje (hasta 60 días), la etapa de tratamiento doble ciego (24 semanas), la etapa de NA únicamente (24 semanas) y las etapas de cese del NA y durabilidad (48 semanas), es de aproximadamente 104 semanas como máximo para cada participante.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Participants who have documented chronic HBV infection ≥6 months prior to screening and currently receiving stable NA therapy defined as no changes to their NA regimen from at least 6 months prior to Screening and with no planned changes to the stable regimen over the duration of the study.
Plasma or serum HBsAg concentration \>100 IU/mL, but no greater than ≤3000 IU/mL.
Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA \<90 IU/mL.
Alanine aminotransferase (ALT) ≤2 × upper limit of normal (ULN).
Participants who are willing and able to cease their NA treatment in accordance with the protocol.

Criterios de exclusión

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 or coagulopathy) or physical examination.
Co-infection with:
a) Current history of Hepatitis C infection or participants that have been cured for \<12 months at the time of screening b) Human immunodeficiency virus (HIV), c) 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 except for specific cancers that are cured by surgical resection (e.g., 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) or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
History of extrahepatic disorders possibly related to HBV immune conditions (e.g., 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 (e.g., 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 enrolment in the study.
Currently taking, or has taken within 12 months of Screening, any interferon containing therapy.
Participants requiring anti coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of the study, by the discretion of the investigator. Occasional use is permitted.
Prior treatment with any oligonucleotide or siRNA within 12 months prior to the first dosing day.
Prior treatment with bepirovirsen.

Estudio multicéntrico aleatorizado, doble ciego de fase 3 para evaluar la eficacia y seguridad del tratamiento con bepirovirsen en participantes con hepatitis B crónica tratados con análogos de nucleós(t)idos (B-Well 2)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Bepirovirsen

Placebo

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores