- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT07852091
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
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Dachuan Cai, MD
- Número de telefone: +86 18323409779
- E-mail: cqmucdc@cqmu.edu.cn
Estude backup de contato
- Nome: Min Chen, PhD
- Número de telefone: +86 17338600343
- E-mail: mchen@hospital.cqmu.edu.cn
Locais de estudo
-
-
Chongqing Municipality
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Chongqing, Chongqing Municipality, China, 400010
- Recrutamento
- The 2nd affiliated Hospital of Chongqing Medical University
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Investigador principal:
- HONG REN, Professor
-
Contato:
- DACHUAN CAI
- Número de telefone: +8618323409779
- E-mail: cqmucdc@cqmu.edu.cn
-
Contato:
- HONG REN
- Número de telefone: +8613983888786
- E-mail: renhong0531@vip.sina.com
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Sign the informed consent form before inclusion and be able to complete the study according to the study requirements;
- 18-60 years old.
- NAs-naive/NAs-experienced CHB patients.
Exclusion Criteria:
- 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;
- Use of inhibitors, inducers or substrates of CYP3A4 within 28 days before enrollment;
- 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;
- Acute infection within 2 weeks before enrollment which requires intravenous antibiotic treatment, or existing infection which requires anti-infection treatment when enrollment;
- Clinically significant acute and chronic liver disease not caused by HBV infection (judged by reseachers);
- 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;
- 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);
- A history of pathological fracture or osteoporosis;
- 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;
- Serious diseases of circulatory, respiratory, urinary, blood, metabolic, immune, mental, neurological, renal and other systems;
- Major trauma or major surgery within 3 months before enrollment, or planned surgery during the study period;
- 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;
- 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);
- Hepatitis C virus (HCV) antibody (+), HIV antigen/antibody (+), or treponema pallidum antibody (+) and rapid plasma regain (RPR) test (+);
- A history of continuous alcohol abuse within 3 years before enrollment (average daily alcohol consumption exceeds 20 gram);
- A history of drug dependence or drug abuse within 1 year before enrollment;
- 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;
- Female in suckling period or pregnancy test (+) during screening;
- Subjects who are considered by the researcher to have other factors that are not suitable for the study
Plano de estudo
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:
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
Colaboradores
Investigadores
- Diretor de estudo: Hong Ren, MM, The Second Affiliated Hospital of Chongqing Medical University
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Infecções transmitidas pelo sangue
- Processos Patológicos
- Doença crônica
- Atributos da doença
- Infecções
- Doenças Virais
- Doenças do aparelho digestivo
- Doenças do Fígado
- Hepatite, Viral, Humana
- Doenças Transmissíveis
- Infecções por vírus de DNA
- Infecções Hepadnaviridae
- Hepatite Crônica
- Hepatite
- Condições Patológicas, Sinais e Sintomas
- Hepatite B
- Hepatite B Crônica
- Enganfolimab
- Sintilimab
Outros números de identificação do estudo
- 2025-0215
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
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