- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01369199
Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (HBRN)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase.
To evaluate safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase.
A single arm treatment study of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal alanine aminotransferase (ALT) levels and high serum levels of hepatitis B virus (HBV) DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants followed for 48 weeks after treatment discontinuation (week 96 for those who completed treatment).
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Ontario
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Toronto, Ontario, Canadá, M5T 2S8
- University of Toronto
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California
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Los Angeles, California, Estados Unidos, 90095
- University of California Los Angeles
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Los Angeles, California, Estados Unidos, 90048
- Cedars Sinai Medical Center
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San Francisco, California, Estados Unidos, 94143
- University of California San Francisco
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San Francisco, California, Estados Unidos, 94115
- California Pacific Medical Center
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Hawaii
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Honolulu, Hawaii, Estados Unidos, 96813
- Queen's Medical Center
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Maryland
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Bethesda, Maryland, Estados Unidos, 20892
- NIH Clinical Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan Health System
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55446
- University of Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63110
- Washington University
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Saint Louis, Missouri, Estados Unidos, 63104
- Saint Louis University
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599
- University of North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke University Medical Center
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Texas
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Dallas, Texas, Estados Unidos, 75390
- University of Texas Southwestern
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Dallas, Texas, Estados Unidos, 75246
- Baylor University Medical Center
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Virginia
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Richmond, Virginia, Estados Unidos, 23498
- Virginia Commonwealth University
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Washington
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Seattle, Washington, Estados Unidos, 98101
- Virginia Mason Medical Center
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Seattle, Washington, Estados Unidos, 98105
- University of Washington Medical Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Enrolled in & completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit.
- >18 years of age at the baseline visit (day 0). Patients >50 years of age at baseline will need to have a liver biopsy as standard of care with hepatic activity index (HAI) ≤3 & Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.
- Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24 weeks prior to baseline visit OR at least one positive HBsAg & negative anti-hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least one positive HBsAg & two positive HBV DNA over a period of ≥24 weeks prior to baseline visit.
- Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.
- Serum HBV DNA level >10˄7 IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before baseline visit. One of the two HBV DNA levels must be within 6 weeks of baseline visit.
- ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the upper limit of normal (ULN) range) as documented by at least three values: one taken 28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit, & the final value within 6 weeks prior to baseline visit.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC surveillance must have negative liver imaging as shown by ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline visit. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging & shown not to have HCC on CT or MRI before they can be enrolled.
Exclusion Criteria:
- History of hepatic decompensation
- Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, international normalization ratio (INR) >1.5, or serum albumin <3.5 g/dL.
- Platelet count <120,000/mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at last screening visit.
- Previous treatment with medications that have established activity against HBV including interferon & nucleos(t)ide analogs ≥24 weeks. Patients with <24 weeks of prior HBV treatment & a wash-out period >24 weeks are not excluded.
- Known allergy or intolerance to study medications.
- Females who are pregnant or breastfeeding. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
- Renal insufficiency with calculated creatinine clearance <50 mL/min at screening.
- History of alcohol or drug abuse within 48 weeks of baseline visit.
- Previous liver or other organ transplantation (including engrafted bone marrow).
- Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis &/or mild to moderate steatohepatitis is acceptable but NAFLD with severe steatohepatitis is exclusionary.
- Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit. Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).
- Pre-existing psychiatric condition(s), including, but not limited to: current moderate or severe depression, history of depression requiring hospitalization within the past 10 years, history of suicidal or homicidal attempt within the past 10 years, history of severe psychiatric disorders as determined by a study physician.
- History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
- Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
- Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
- Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
- Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
- Concomitant use of complementary or alternative medications purported to have antiviral activity.
- Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
Plan de estudios
¿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 |
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Experimental: Peginterferon and entecavir
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
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Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Incidencia de eventos adversos graves (SAE) por persona-año
Periodo de tiempo: Desde el primer tratamiento hasta el final del tratamiento (hasta 48 semanas) y el final del seguimiento (hasta 96 semanas)
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La incidencia se calcula como el número de EAG dividido por el número de años-persona de observación, que es la suma, entre todos los participantes, del número de años entre el inicio y el final del tratamiento, o el final del seguimiento. -arriba, respectivamente.
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Desde el primer tratamiento hasta el final del tratamiento (hasta 48 semanas) y el final del seguimiento (hasta 96 semanas)
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Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL
Periodo de tiempo: End of follow-up (up to 96 weeks)
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Lack of data was considered to be treatment failure.
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End of follow-up (up to 96 weeks)
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Incidence of Adverse Events (AEs) Per Person-Year of Observation
Periodo de tiempo: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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The number of AEs includes both AEs and Serious Adverse Events (SAEs).
The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
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From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Proporción de participantes con seroconversión HBeAg
Periodo de tiempo: Fin del tratamiento (hasta 48 semanas)
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Fin del tratamiento (hasta 48 semanas)
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Proporción de participantes con seroconversión HBeAg
Periodo de tiempo: Fin del seguimiento (hasta 96 semanas)
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Fin del seguimiento (hasta 96 semanas)
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Proporción de participantes con seroconversión de HBsAg
Periodo de tiempo: Fin del tratamiento (hasta 48 semanas)
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Fin del tratamiento (hasta 48 semanas)
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Proporción de participantes con seroconversión de HBsAg
Periodo de tiempo: Fin del seguimiento (hasta 96 semanas)
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Fin del seguimiento (hasta 96 semanas)
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Proporción de participantes con ADN del VHB ≤1000 UI/mL
Periodo de tiempo: Fin del tratamiento (hasta 48 semanas)
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Fin del tratamiento (hasta 48 semanas)
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Proporción de participantes con ADN del VHB ≤1000 UI/mL
Periodo de tiempo: Fin del seguimiento (hasta 96 semanas)
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Fin del seguimiento (hasta 96 semanas)
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Proportion of Participants With HBeAg Loss
Periodo de tiempo: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBeAg Loss
Periodo de tiempo: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBsAg Loss
Periodo de tiempo: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBsAg Loss
Periodo de tiempo: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With Alanine Aminotransferase (ALT) <45 U/L for Men, <30 U/L for Women
Periodo de tiempo: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT <45 U/L for Men, <30 U/L for Women
Periodo de tiempo: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
Periodo de tiempo: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
Periodo de tiempo: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
Periodo de tiempo: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
Periodo de tiempo: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Absence of Detectable Antiviral Drug-resistance HBV Mutations
Periodo de tiempo: End of treatment (up to 48 weeks)
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HBV drug resistance variant testing was performed at the CDC laboratory.
The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing.
Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.
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End of treatment (up to 48 weeks)
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Colaboradores e Investigadores
Investigadores
- Silla de estudio: Averell Sherker, MD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Investigador principal: Anna Lok, MD, University of Michigan
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Infecciones por virus de ARN
- Enfermedades virales
- 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 Crónica
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B Crónica
- Agentes antiinfecciosos
- Agentes Antivirales
- Peginterferón alfa-2a
- Entecavir
Otros números de identificación del estudio
- DK082864 HBRN IT Adult Trial
- UL1RR024986 (Subvención/contrato del NIH de EE. UU.)
- UL1TR001111 (Subvención/contrato del NIH de EE. UU.)
- U01DK082916 (Subvención/contrato del NIH de EE. UU.)
- U01DK082864 (Subvención/contrato del NIH de EE. UU.)
- U01DK082874 (Subvención/contrato del NIH de EE. UU.)
- U01DK082944 (Subvención/contrato del NIH de EE. UU.)
- U01DK082843 (Subvención/contrato del NIH de EE. UU.)
- U01DK082871 (Subvención/contrato del NIH de EE. UU.)
- UL1TR000004 (Subvención/contrato del NIH de EE. UU.)
- A-DK-3002-001 (Otro número de subvención/financiamiento: Interagency agreement with NIDDK)
- U01DK082863 (Subvención/contrato del NIH de EE. UU.)
- U01DK082866 (Subvención/contrato del NIH de EE. UU.)
- U01DK082867 (Subvención/contrato del NIH de EE. UU.)
- U01DK082872 (Subvención/contrato del NIH de EE. UU.)
- U01DK082919 (Subvención/contrato del NIH de EE. UU.)
- U01DK082923 (Subvención/contrato del NIH de EE. UU.)
- U01DK082927 (Subvención/contrato del NIH de EE. UU.)
- U01DK082943 (Subvención/contrato del NIH de EE. UU.)
- UL1TR000058 (Subvención/contrato del NIH de EE. UU.)
- P30DK050306 (Subvención/contrato del NIH de EE. UU.)
- M01RR000040 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Hepatitis B
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The Affiliated Nanjing Drum Tower Hospital of Nanjing...Gilead SciencesAún no reclutando
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Nanfang Hospital of Southern Medical UniversityReclutamiento
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IlDong Pharmaceutical Co LtdReclutamientoHepatitis b crónicaCorea, república de
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Antios Therapeutics, IncTerminadoHepatitis b crónicaEstados Unidos
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Xi'an Xintong Pharmaceutical Research Co.,Ltd.Desconocido
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Tongji HospitalChia Tai Tianqing Pharmaceutical Group Co., Ltd.DesconocidoHepatitis b crónica
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Tongji HospitalGilead SciencesReclutamiento
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Jiangsu HengRui Medicine Co., Ltd.Desconocido
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Changhai HospitalTerminadoHepatitis b crónicaPorcelana
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National Taiwan University HospitalChiayi Christian Hospital; E-DA Hospital; Taipei City Hospital; Taipei Tzu Chi Hospital... y otros colaboradoresReclutamientoHepatitis b crónica | Reactivación de Hepatitis BTaiwán
Ensayos clínicos sobre Entecavir and peginterferon
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University Hospitals Cleveland Medical CenterDesconocidoAsma | Rinitis alérgica | Conjuntivitis alérgicaEstados Unidos
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Biosplice Therapeutics, Inc.Terminado
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University of Southern CaliforniaTerminadoEnfermedad del simuladorEstados Unidos
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Dalarna UniversityUppsala University; The Swedish Research CouncilReclutamientoDemencia | Defecto cognitivo leve | Demencia Mixta | Demencia de tipo Alzheimer | Deterioro Cognitivo Subjetivo | Demencia senilSuecia
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Eunice Kennedy Shriver National Institute of Child...Desconocido
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ShuGuang HospitalBeijing YouAn Hospital; Beijing Ditan Hospital; Shanghai Zhongshan Hospital; Tongji... y otros colaboradoresDesconocidoCirrosis hepática debida al virus de la hepatitis BPorcelana
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Beijing Friendship HospitalPeking University; Peking University First Hospital; Peking University People's... y otros colaboradoresTerminadoFibrosis hepáticaPorcelana
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Northeastern UniversityFlorida State University; Florida A&M UniversityAún no reclutandoSíntomas depresivos subclínicosEstados Unidos
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Institut de Cancérologie de la LoireTerminado
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Sunshine Lake Pharma Co., Ltd.Suspendido