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Antiviral Efficacy of Switching to ETV Plus TDF

30 de enero de 2014 actualizado por: Sang Hoon Ahn, Yonsei University

A Randomized, Multicenter, Prospective Study to Compare Antiviral Efficacy and Safety of Switching to ETV Plus TDF Versus Maintaining LAM/LDT Plus ADF Combination in CHC With PVR to LAM/LDF Plus ADF Combination Rescue Therapy for YMDD Mutation

Switching to Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will result in faster and greater antiviral activity and lower rates of resistance emergence over maintaining Lamivudine(LAM)/Telbivudine(LdT)+Adefovir(ADV) combination in partial responders to LAM/LdT+ADV rescue therapy.

Earlier switching to combination with the most potent regimen will be more effective to achieve virologic response(VR) and prevent further resistance emergence.

All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Descripción general del estudio

Estado

Desconocido

Condiciones

Intervención / Tratamiento

Descripción detallada

  1. As TDF has not been approved yet in Korea, current KASL practice guideline generally recommends to add ADV in LAM-resistant or LdT-resistant patients.
  2. However, several local literatures reported a substantial proportion of patients treated with LAM plus ADV combination therapy showed a persistently inadequate or partial virologic response('VR') and YMDDm still maintained in spite of under rescue combination therapy.
  3. Due to the unavailability of TDF in Korea, ETV plus ADV combination has being considered a better salvage therapy with non-overlapping cross-resistance profiles in pts who fail to LAM plus ADV rescue therapy and local report demonstrated that the rate of VR was significantly higher with ETV+ADV switching group than LAM+ADV continuation group in partial responder to LAM plus ADV combination rescue therapy for LAM resistance.
  4. Hence, more earlier combination therapy with the most potent Nucleoside and Nucleotide analogue would be a promising salvage treatment for previous NA treatment failures but comparative prospective trials are limited.
  5. Therefore, this study will investigate the greater effectiveness and safety of switching to the most potent combination versus maintaining LAM(or LdT) plus ADV and also compare the rate of VR based on the HBV DNA cut-off level at switching - more than and less than 20,000 IU/mL.

All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Tipo de estudio

Intervencionista

Inscripción (Anticipado)

104

Fase

  • Fase 4

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

20 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. ≥ 20 years of age
  2. History of HBsAg positive for more than 6 months
  3. History of genotypic resistance to LAM or LdT (YMDDm)
  4. Partial responder (HBV DNA ≥ 60 IU/mL) currently receiving antiviral combination rescue therapy for at least 24 weeks of treatment with LAM+ADV or LdT+ADV
  5. Hepatitis B e Antigen(HBeAg)-positive and -negative
  6. Compensated liver disease (Child-Pugh A)
  7. Signed written informed consent after being instructed about the objective and procedure of the clinical study

Exclusion Criteria:

  1. History of genotypic resistance to ADV
  2. Most previous treatment of other than LAM+ADV and LdT+ADV
  3. Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)
  4. Co-infected with hepatitis C virus(HCV) or HIV
  5. Pregnant or lactating woman
  6. Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion
  7. History of liver transplantation or planned for liver transplantation
  8. Subject who was diagnosed malignant tumor and has been receiving chemotherapy
  9. Subject who has HCC history or who shows potential hepatocellular carcinoma (HCC) finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
  10. Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
  11. Subject who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.)
  12. Subject who has a history of hypersensitivity to study drug or its ingredients
  13. Subject who is involved in other clinical trial within 60 days prior to study entry
  14. Subject who the investigator deems inappropriate to participate in this study

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Group A:
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
Droga: Group A (Zeffix, Sebivo, Hepsera)
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
Otros nombres:
  • Hepsera
  • Sebivo
  • Zeffix
Experimental: Group B
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg
Droga: Group B (Baraclude, Viread)
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg
Otros nombres:
  • Viread
  • Baraclude

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48
Periodo de tiempo: at Week 48
To compare the proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) in switching group(Entecavir plus Tenofovir) with that in maintaining group(Lamivudine/Telbivudine plus Adefovir) by real-time Polymerase chain reaction(PCR) at Week 48
at Week 48

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Virologic efficacy
Periodo de tiempo: Week 12, 24, 36, and 48
To compare virologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
Week 12, 24, 36, and 48
serologic efficacy
Periodo de tiempo: Week 12, 24, 36, and 48
To compare serologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
Week 12, 24, 36, and 48
biochemical efficacy
Periodo de tiempo: Week 12, 24, 36, and 48
To compare biochemical response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
Week 12, 24, 36, and 48
Safety issue
Periodo de tiempo: Week 12, 24, 36, and 48
To compare safety issue in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48 - severity of adverse event
Week 12, 24, 36, and 48

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Yonsei University

Colaboradores

Bristol-Myers Squibb
Chonbuk National University Hospital
Seoul St. Mary's Hospital
Pusan National University Hospital
Kyungpook National University Hospital
The Catholic University of Korea
Soonchunhyang University Hospital
Hallym University Medical Center

Investigadores

  • Investigador principal: Sang Hoon Ahn, MD, PhD, Yonsei University

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de agosto de 2012

Finalización primaria (Anticipado)

1 de mayo de 2014

Finalización del estudio (Anticipado)

1 de mayo de 2014

Fechas de registro del estudio

Enviado por primera vez

8 de mayo de 2012

Primero enviado que cumplió con los criterios de control de calidad

14 de mayo de 2012

Publicado por primera vez (Estimar)

15 de mayo de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

31 de enero de 2014

Última actualización enviada que cumplió con los criterios de control de calidad

30 de enero de 2014

Última verificación

1 de enero de 2014

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • AI463-274

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