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A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (A)

29 de septiembre de 2026 actualizado por: The Second Affiliated Hospital of Chongqing Medical University

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferonα (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. Programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1/anti-PD-L1 antibody) and IFNα in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Estimado)

1200

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Dachuan Cai, MD
  • Número de teléfono: +86 18323409779
  • Correo electrónico: cqmucdc@cqmu.edu.cn

Copia de seguridad de contactos de estudio

Ubicaciones de estudio

    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, Porcelana, 400010
        • Reclutamiento
        • The 2nd affiliated Hospital of Chongqing Medical University
        • Investigador principal:
          • HONG REN, Professor
        • Contacto:
        • Contacto:

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

18 años a 60 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Sign the informed consent form before inclusion and be able to complete the study according to the study requirements;
  2. 18-60 years old.
  3. NAs-naive/NAs-experienced CHB patients.

Exclusion Criteria:

  1. A history of allergy, or who are suspected by the researcher to be allergic to the active ingredient of the drug under study or its excipients;
  2. Use of inhibitors, inducers or substrates of CYP3A4 within 28 days before enrollment;
  3. Systematical use of immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before enrollment, or vaccination of live attenuated vaccine within 1 month before enrollment;
  4. Acute infection within 2 weeks before enrollment which requires intravenous antibiotic treatment, or existing infection which requires anti-infection treatment when enrollment;
  5. Clinically significant acute and chronic liver disease not caused by HBV infection (judged by reseachers);
  6. Confirmed or suspected decompensated cirrhosis, including but not limited to: hepatic encephalopathy, hepatorenal syndrome, bleeding from esophageal varices, splenomegaly, ascites, etc, or evidence of progressive liver fibrosis;
  7. Primary liver cancer, or alpha-fetoprotein (AFP) is greater than 50 ug/L or imaging suggests the possibility of malignant liver lesions, or other malignant tumors or a history of other malignant tumors within 5 years before enrollment (except that the malignant tumors have been completely relieved after treatment and patients have not received additional medical or surgical intervention within 3 years before screening);
  8. A history of pathological fracture or osteoporosis;
  9. Gastrointestinal dysfunction or gastrointestinal diseases that might affect the absorption of oral drugs, such as severe gastric ulcer, erosive gastritis, partial gastrectomy, and persistent gastrointestinal symptoms (such as nausea, vomiting, or diarrhea) >2 grades;
  10. Serious diseases of circulatory, respiratory, urinary, blood, metabolic, immune, mental, neurological, renal and other systems;
  11. Major trauma or major surgery within 3 months before enrollment, or planned surgery during the study period;
  12. Blood donation/loss ≥ 400 mL within 3 months before enrollment, or given a blood transfusion within 3 months before enrollment, or blood donation/loss ≥ 200 mL within 1 month before enrollment;
  13. Platelet count<90 × 10^9/L, white blood cell count<3.0 × 10^9/L, neutrophil count<1.3 × 10^9/L, total serum bilirubin>2 × upper limit of normal (ULN), albumin<30 g/L, creatinine clearance ≤ 60 mL/min (calculated by CKD-EPI formula), or international normalized ratio of prothrombin time (INR)>1.5 (unless receiving stable anticoagulant therapy);
  14. Hepatitis C virus (HCV) antibody (+), HIV antigen/antibody (+), or treponema pallidum antibody (+) and rapid plasma regain (RPR) test (+);
  15. A history of continuous alcohol abuse within 3 years before enrollment (average daily alcohol consumption exceeds 20 gram);
  16. A history of drug dependence or drug abuse within 1 year before enrollment;
  17. Those who have participated in clinical trials of other investigational drugs or medical devices and taken investigational drugs or used medical devices within 3 months before enrollment;
  18. Female in suckling period or pregnancy test (+) during screening;
  19. Subjects who are considered by the researcher to have other factors that are not suitable for the 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: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: NAs combined with Sintilimab/Envafolimab

NAs (Once/day, 1 capsule/time, oral)combined with Sintilimab(anti-PD-1 antibody, once/three weeks, dose lower than the dose used in cancer patients, intravenous injection) /Envafolimab(anti-PD-L1 antibody, once/two weeks, dose lower than the dose used in cancer patients, subcutaneous injection), followed by NAs monotherapy

Sintilimab(anti-PD-1 antibody),once/three weeks, dose lower than the dose used in cancer patients, intravenous injection; Envafolimab(anti-PD-L1 antibody),once/two weeks, dose lower than the dose used in cancer patients, subcutaneous injection

Otros nombres:
  • Sintilimab(anti-PD-1 antibody)
  • Envafolimab(anti-PD-L1 antibody)

NAs(ETV/TDF/TAF), Once/day, 1 capsule/time, oral

Comparador activo: NAs

NAs(Once/day, 1 capsule/time, oral)

NAs(ETV/TDF/TAF), Once/day, 1 capsule/time, oral

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Serum HBsAg
Periodo de tiempo: Baseline

Serum HBsAg level

Baseline
Serum HBsAg
Periodo de tiempo: 24 weeks after the treatment

Serum HBsAg level

24 weeks after the treatment
Serum HBsAg
Periodo de tiempo: 48 weeks after the treatment

Serum HBsAg level

48 weeks after the treatment
Serum HBsAg
Periodo de tiempo: 24 weeks after the end of treatment

Serum HBsAg level

24 weeks after the end of treatment
Serum HBV DNA
Periodo de tiempo: Baseline

Serum HBV DNA level

Baseline
Serum HBV DNA
Periodo de tiempo: 24 weeks after the treatment

Serum HBV DNA level

24 weeks after the treatment
Serum HBV DNA
Periodo de tiempo: 48 weeks after the treatment

Serum HBV DNA level

48 weeks after the treatment
Serum HBV DNA
Periodo de tiempo: 24 weeks after the end of treatment

Serum HBV DNA level

24 weeks after the end of treatment
Serum alanine aminotransferase (ALT)
Periodo de tiempo: Baseline

Serum ALT level

Baseline
Serum alanine aminotransferase (ALT)
Periodo de tiempo: 24 weeks after the treatment

Serum ALT level

24 weeks after the treatment
Serum alanine aminotransferase (ALT)
Periodo de tiempo: 48 weeks after the treatment

Serum ALT level

48 weeks after the treatment
Serum alanine aminotransferase (ALT)
Periodo de tiempo: 24 weeks after the end of treatment

Serum ALT level

24 weeks after the end of treatment

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Periodo de tiempo: Baseline

Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)

Baseline
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Periodo de tiempo: 24 weeks after the treatment

Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)

24 weeks after the treatment
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Periodo de tiempo: 48 weeks after the treatment

Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)

48 weeks after the treatment
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Periodo de tiempo: 24 weeks after the end of treatment

Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)

24 weeks after the end of treatment
Immune response of T and B cells
Periodo de tiempo: Baseline

Frequencies and functions of T and B cells (tested by flowcytometry/FluoroSpot/ELISPOT)

Baseline
Immune response of T and B cells
Periodo de tiempo: 24 weeks after the treatment

Frequencies and functions of T and B cells (tested by flowcytometry/FluoroSpot/ELISPOT)

24 weeks after the treatment
Immune response of T and B cells
Periodo de tiempo: 48 weeks after the treatment

Frequencies and functions of T and B cells (tested by flowcytometry/FluoroSpot/ELISPOT)

48 weeks after the treatment
Immune response of T and B cells
Periodo de tiempo: 24 weeks after the end of treatment

Frequencies and functions of T and B cells (tested by flowcytometry/FluoroSpot/ELISPOT)

24 weeks after the end of treatment
Virus and host genome
Periodo de tiempo: Baseline

Detect virus and host genome using peripheral blood and liver tissue by sequencing

Baseline
Virus and host genome
Periodo de tiempo: 24 weeks after the treatment

Detect virus and host genome using peripheral blood and liver tissue by sequencing

24 weeks after the treatment
Virus and host genome
Periodo de tiempo: 48 weeks after the treatment

Detect virus and host genome using peripheral blood and liver tissue by sequencing

48 weeks after the treatment
Virus and host genome
Periodo de tiempo: 24 weeks after the end of treatment

Detect virus and host genome using peripheral blood and liver tissue by sequencing

24 weeks after the end of treatment

Colaboradores e Investigadores

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

Patrocinador

Colaboradores

Investigadores

  • Director de estudio: Hong Ren, MM, The Second Affiliated Hospital of Chongqing Medical University

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 (Actual)

10 de octubre de 2023

Finalización primaria (Estimado)

31 de diciembre de 2026

Finalización del estudio (Estimado)

31 de diciembre de 2026

Fechas de registro del estudio

Enviado por primera vez

21 de septiembre de 2026

Primero enviado que cumplió con los criterios de control de calidad

29 de septiembre de 2026

Publicado por primera vez (Actual)

1 de octubre de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

1 de octubre de 2026

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

29 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • 2025-0215

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

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. .