- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02474316
Combined Therapy With Peginterferon Alfa-2a With NA in NA-treated HBeAg Positive Patients
A Prospective, Randomized, Multicenter, Open-label Study Evaluating HBeAg Seroconversion in HBeAg Positive CHB Patients on Treatment With NA Switched to Combined Therapy With Peginterferon Alfa-2a and NA for 48 Weeks
This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:
Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1 piece qd for 48 weeks Arm B: Entecavir 0.5mg qd for 48 weeks
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:
Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1piece qd for 48 weeks Arm B:NA 1 piece qd for 48 weeks
The primary endpoint: HBeAg seroconversion at week 48
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Qing Xie
- Número de teléfono: 86-13651804273
- Correo electrónico: xieqingrjh2015@gmail.com
Ubicaciones de estudio
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-
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Guilin, Porcelana
- Reclutamiento
- The Third People's Hospital of Guilin
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Contacto:
- Shuquan Chen, doctor
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Shanghai, Porcelana
- Reclutamiento
- Ruijin Hospital
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Contacto:
- Qing Xie, doctor
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Contacto:
- Wei Cai, doctor
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Shanghai, Porcelana
- Reclutamiento
- Shanghai Public Health Clinical Center
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Contacto:
- Liang Chen, doctor
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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:
- Male and female patients with age ≥18 and ≤65 years;
- There should be evidences that HBsAg and HBeAg have been positive for more than 6 months with HBsAb and HBeAb negative before treated with Entecavir;
- Treated with NA for more than 24 weeks and achieve HBV DNA<1000copies/ml with HBeAb negative;
- Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment
- Agree to participate in the study and sign the patient informed consent.
Exclusion Criteria:
- Co-infection with active hepatitisA, hepatitisC, hepatitisD and/or human immunodeficiency virus (HIV)
- AFP>50ng/ml and/or evidence of hepatocellular carcinoma
Evidence of decompensated liver disease (Child-Pugh scores >5). Child-Pugh >5 means that, if one of the following 6 conditions is met, the patient has to be excluded:
- Serum albumin <35 g/L;
- Prothrombine time prolonged≥ 4 seconds or PTA < 60%;
- Serum bilirubin > 34 µmol/L;
- History of encephalopathy;
- Ascites
- History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia)
- Pregnant or breast-feeding Women
- ANC<1.5x 10^9/L or PLT<90x 10^9/L
- Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment
- History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
- History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)
- History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease
- History of chronic pulmonary disease associated with functional limitation
- History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)
- Hemodialysis patients or patients with renal insufficiency
- History of a severe seizure disorder or current anticonvulsant use
- Major organ transplantation or other evidence of severe illness, malignancy, or any other conditions, which would make the patient, in the opinion of the investigator, unsuitable for the study
- History of thyroid disease poorly controlled on prescribed medications
- Evidence of severe retinopathy or clinically relevant ophthalmologic disorder
- History of other severe disease or evidence of other severe disease or any other illness or conditions that the investigator believe that patients are not suitable to join in the study
- Immunomodulatory treatment (including interferon) or LDT within 1 year prior to the first dose of treatment
- Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening
Plan de estudios
¿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 |
---|---|
Experimental: PegINF plus nucleos(i)de analgoue
Peginterferon alfa-2a 180μg /wk plus nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks
|
Peginterferon alfa-2a 180ug/wk s.c for 48 weeks
Otros nombres:
nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks
|
Comparador activo: nucleos(t)ide analgoue
nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks
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nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Number of participants who achieve HBeAg seroconversion
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the HBeAg seroconversion in HBeAg positive CHB patients on treatment with Entecavir and with HBV DNA <1000copies/ml which will be measured by the number of participants who achieve HBeAg seroconversion
|
at week 48
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Number of participants who achieve HBeAg loss
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBeAg seroconversion which will be measured by number of participants who achieve HBeAg loss
|
at week 48
|
Number of participants who achieve HBsAg loss
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg loss which will be measured by number of participants who achieve HBsAg loss
|
at week 48
|
Number of participants who achieve HBsAg seroconversion
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg seroconversion which will be measured by number of participants who achieve HBsAg seroconversion
|
at week 48
|
HBsAg decline from baseline
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg decline from baseline
|
at week 48
|
Percentage of participants who achieve HBsAg <1000IU/mL
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of participants who achieve HBsAg<1000IU/mL
|
at week 48
|
Percentage of of participants who achieve HBsAg <100IU/mL
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of of participants who achieve HBsAg<100IU/mL
|
at week 48
|
Number of participants who achieve combined response I (defined as HBeAg seroconversion and HBV DNA<100000copies/mL)
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response I which will be measured by number of participants who achieve combined response I
|
at week 48
|
Number of participants who achieve combined response II (defined as HBeAg seroconversion and HBV DNA<1000copies/mL)
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response II which will be measured by number of participants who achieve combined response II
|
at week 48
|
Number of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<1000IU/mL)
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response I which will be measured by number of participants who achieve dural response I
|
at week 48
|
Number of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<100IU/mL)
Periodo de tiempo: at week 48
|
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response II which will be measured by number of participants who achieve dural response II
|
at week 48
|
Number of Participants with AE
Periodo de tiempo: at week 48
|
Number of participants with adverse events as a measure of safety and tolerability
|
at week 48
|
Number of Participants with SAE
Periodo de tiempo: at week 48
|
Number of participants with SAEs as a measure of safety and tolerability
|
at week 48
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Qing Xie, Ruijin Hospital
Publicaciones y enlaces útiles
Publicaciones Generales
- Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010 Feb;51(2):422-30. doi: 10.1002/hep.23327.
- Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014 Dec 6;384(9959):2053-63. doi: 10.1016/S0140-6736(14)60220-8. Epub 2014 Jun 18.
- Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology. 2015 May;61(5):1512-22. doi: 10.1002/hep.27586. Epub 2015 Feb 27.
- Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003 Dec 20;362(9401):2089-94. doi: 10.1016/S0140-6736(03)15108-2.
- Tassopoulos NC, Volpes R, Pastore G, Heathcote J, Buti M, Goldin RD, Hawley S, Barber J, Condreay L, Gray DF. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. Hepatology. 1999 Mar;29(3):889-96. doi: 10.1002/hep.510290321.
- Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):808-16. doi: 10.1056/NEJMoa020681.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
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 (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Enfermedades virales
- Infecciones
- Infecciones transmitidas por la sangre
- Enfermedades contagiosas
- Enfermedades del HIGADO
- Hepatitis, Viral, Humana
- Infecciones por Hepadnaviridae
- Infecciones por virus de ADN
- Hepatitis Crónica
- Hepatitis
- Hepatitis B
- Hepatitis B Crónica
- Agentes antiinfecciosos
- Agentes Antivirales
- Peginterferón alfa-2a
Otros números de identificación del estudio
- HOPE
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. .
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