Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection
30 de enero de 2014 actualizado por: Sang Hoon Ahn, Yonsei University
A Multicenter, Open-label, Prospective Study to Evaluate Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection
Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will show effective antiviral activity and prevent further development of antiviral resistance in hepatitis B e antigen(HBeAg)-positive or -negative Chronic Hepatitis B(CHB) patients who experienced multidrug resistance
All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. 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
- It has been one of unsolved issues and unmet needs in CHB management to develop an optimal combination regimen to manage multidrug resistant HBV characterized by selection of variants with two or more classes A of signature genotypic resistant mutations1-3
- Currently adding on Adefovir(ADV) has been generally recommended in Lamivudine(LAM)- or Telbivudine(LdT)-resistant patients but little is known about the optimal management of CHB patients who developed multidrug resistance4
- Recent report has shown that the combination of LAM plus ADV did not suppress HBV DNA effectively in CHB patients with resistance mutations to both drugs. Only 12.2% of these pts achieved virologic response(VR; HBV DNA <60 IU/mL) at 12 months and multivariable analysis showed that LAM+ADV group and the presence of the rtA181V/T mutation were independently associated with a decreased rate of virologic response (HBV DNA <2,000 IU/ml) at 12 months4
- ETV has been demonstrated to be effective in patients with ADV resistance but not in patients with proven YMDD mutation. In contrast, TDF has been shown to be effective in patients with YMDD mutation but not necessarily in all patients with ADV resistance.1-3
- Thus theoretically, the combination of the most potent nucleoside analogue and nucleotide analogue with non-overlapping resistance profiles, such as ETV plus TDF, is expected to be a promising salvage treatment for multidrug resistant HBV but clinical evidence is limited
- Therefore, this study will explore that adequate management of multidrug resistant patients using ETV plus TDF combination may lead to faster and greater viral suppression and prevent further emergence of antiviral resistance
All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. 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)
90
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:
- ≥ 20 years of age
- History of HBsAg positive for more than 6 months
- Subject who has a history of genotypic resistance to NAs from two different classes A
- Detectable HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks
- HBeAg-positive and -negative
- Compensated liver disease (Child-Pugh A)
- Signed written informed consent after being instructed about the objective and procedure of the clinical study
Exclusion Criteria:
- Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)
- Co-infected with hepatitis C virus(HCV) or HIV
- Pregnant or lactating woman
- 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
- History of liver transplantation or planned for liver transplantation
- Subject who was diagnosed malignant tumor and has been receiving chemotherapy
- Subject who has hepatocellular carcinoma(HCC) history or who shows potential HCC finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
- Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
- Patient 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.)
- Subject who has a history of hypersensitivity to study drug or its ingredients
- Subject who is involved in other clinical trial within 60 days prior to study entry
- 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: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Entecavir 1.0mg + Tenofovir 300mg
All subjects will orally take investigational drugs once daily for 48 weeks.
|
Entecavir 1.0mg + Tenofovir 300mg
Otros nombres:
|
¿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 evaluate the proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time Polymerase chain reaction(PCR) at Week 48 after Entecavir plus Tenofovir combination therapy
|
at Week 48
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Virologic, serologic, biochemical efficacy and safety profile, as measured by the incidence of clinical adverse events and laboratory abnormalities including renal marker
Periodo de tiempo: Week 4, 12, 24, 36, and 48
|
To evaluate virologic, serologic and biochemical response and safety of Entecavir plus Tenofovir combination therapy for 48 weeks
|
Week 4, 12, 24, 36, and 48
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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.
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 abril de 2014
Finalización del estudio (Anticipado)
1 de abril de 2014
Fechas de registro del estudio
Enviado por primera vez
7 de mayo de 2012
Primero enviado que cumplió con los criterios de control de calidad
8 de mayo de 2012
Publicado por primera vez (Estimar)
9 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
- Enfermedades del Sistema Digestivo
- Infecciones por virus de ARN
- Infecciones
- Infecciones transmitidas por la sangre
- Enfermedades contagiosas
- Enfermedades del HIGADO
- Hepatitis, Viral, Humana
- Infecciones por Hepadnaviridae
- Infecciones por virus de ADN
- Infecciones por enterovirus
- Infecciones por Picornaviridae
- Hepatitis B
- Hepatitis
- Hepatitis A
- Enfermedades virales
- Hepatitis B Crónica
- Hepatitis Crónica
- Infecciones por herpesviridae
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de la transcriptasa inversa
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes Anti-VIH
- Agentes antirretrovirales
- Tenofovir
- Entecavir
Otros números de identificación del estudio
- AI463-273
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