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

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).

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Estimado)

1200

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 400010
        • Recrutamento
        • The 2nd affiliated Hospital of Chongqing Medical University
        • Investigador principal:
          • HONG REN, Professor
        • Contato:
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 60 anos (Adulto)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
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

Outros nomes:
  • Sintilimab(anti-PD-1 antibody)
  • Envafolimab(anti-PD-L1 antibody)

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

Comparador Ativo: NAs

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

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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Serum HBsAg
Prazo: Baseline

Serum HBsAg level

Baseline
Serum HBsAg
Prazo: 24 weeks after the treatment

Serum HBsAg level

24 weeks after the treatment
Serum HBsAg
Prazo: 48 weeks after the treatment

Serum HBsAg level

48 weeks after the treatment
Serum HBsAg
Prazo: 24 weeks after the end of treatment

Serum HBsAg level

24 weeks after the end of treatment
Serum HBV DNA
Prazo: Baseline

Serum HBV DNA level

Baseline
Serum HBV DNA
Prazo: 24 weeks after the treatment

Serum HBV DNA level

24 weeks after the treatment
Serum HBV DNA
Prazo: 48 weeks after the treatment

Serum HBV DNA level

48 weeks after the treatment
Serum HBV DNA
Prazo: 24 weeks after the end of treatment

Serum HBV DNA level

24 weeks after the end of treatment
Serum alanine aminotransferase (ALT)
Prazo: Baseline

Serum ALT level

Baseline
Serum alanine aminotransferase (ALT)
Prazo: 24 weeks after the treatment

Serum ALT level

24 weeks after the treatment
Serum alanine aminotransferase (ALT)
Prazo: 48 weeks after the treatment

Serum ALT level

48 weeks after the treatment
Serum alanine aminotransferase (ALT)
Prazo: 24 weeks after the end of treatment

Serum ALT level

24 weeks after the end of treatment

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Prazo: Baseline

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

Baseline
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: Baseline

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

Baseline
Immune response of T and B cells
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: Baseline

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

Baseline
Virus and host genome
Prazo: 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
Prazo: 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
Prazo: 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

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Colaboradores

Investigadores

  • Diretor de estudo: Hong Ren, MM, The Second Affiliated Hospital of Chongqing Medical University

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

10 de outubro de 2023

Conclusão Primária (Estimado)

31 de dezembro de 2026

Conclusão do estudo (Estimado)

31 de dezembro de 2026

Datas de inscrição no estudo

Enviado pela primeira vez

21 de setembro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

29 de setembro de 2026

Primeira postagem (Real)

1 de outubro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

1 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

29 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Outros números de identificação do estudo

  • 2025-0215

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .