- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica 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).
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
Contatti e Sedi
Contatto studio
- Nome: Dachuan Cai, MD
- Numero di telefono: +86 18323409779
- Email: cqmucdc@cqmu.edu.cn
Backup dei contatti dello studio
- Nome: Min Chen, PhD
- Numero di telefono: +86 17338600343
- Email: mchen@hospital.cqmu.edu.cn
Luoghi di studio
-
-
Chongqing Municipality
-
Chongqing, Chongqing Municipality, Cina, 400010
- Reclutamento
- The 2nd affiliated Hospital of Chongqing Medical University
-
Investigatore principale:
- HONG REN, Professor
-
Contatto:
- DACHUAN CAI
- Numero di telefono: +8618323409779
- Email: cqmucdc@cqmu.edu.cn
-
Contatto:
- HONG REN
- Numero di telefono: +8613983888786
- Email: renhong0531@vip.sina.com
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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
Altri nomi:
NAs(ETV/TDF/TAF), Once/day, 1 capsule/time, oral |
|
Comparatore attivo: NAs
NAs(Once/day, 1 capsule/time, oral) |
NAs(ETV/TDF/TAF), Once/day, 1 capsule/time, oral |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Serum HBsAg
Lasso di tempo: Baseline
|
Serum HBsAg level |
Baseline
|
|
Serum HBsAg
Lasso di tempo: 24 weeks after the treatment
|
Serum HBsAg level |
24 weeks after the treatment
|
|
Serum HBsAg
Lasso di tempo: 48 weeks after the treatment
|
Serum HBsAg level |
48 weeks after the treatment
|
|
Serum HBsAg
Lasso di tempo: 24 weeks after the end of treatment
|
Serum HBsAg level |
24 weeks after the end of treatment
|
|
Serum HBV DNA
Lasso di tempo: Baseline
|
Serum HBV DNA level |
Baseline
|
|
Serum HBV DNA
Lasso di tempo: 24 weeks after the treatment
|
Serum HBV DNA level |
24 weeks after the treatment
|
|
Serum HBV DNA
Lasso di tempo: 48 weeks after the treatment
|
Serum HBV DNA level |
48 weeks after the treatment
|
|
Serum HBV DNA
Lasso di tempo: 24 weeks after the end of treatment
|
Serum HBV DNA level |
24 weeks after the end of treatment
|
|
Serum alanine aminotransferase (ALT)
Lasso di tempo: Baseline
|
Serum ALT level |
Baseline
|
|
Serum alanine aminotransferase (ALT)
Lasso di tempo: 24 weeks after the treatment
|
Serum ALT level |
24 weeks after the treatment
|
|
Serum alanine aminotransferase (ALT)
Lasso di tempo: 48 weeks after the treatment
|
Serum ALT level |
48 weeks after the treatment
|
|
Serum alanine aminotransferase (ALT)
Lasso di tempo: 24 weeks after the end of treatment
|
Serum ALT level |
24 weeks after the end of treatment
|
Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Lasso di tempo: Baseline
|
Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb) |
Baseline
|
|
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: Baseline
|
Frequencies and functions of T and B cells (tested by flowcytometry/FluoroSpot/ELISPOT) |
Baseline
|
|
Immune response of T and B cells
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Baseline
|
Detect virus and host genome using peripheral blood and liver tissue by sequencing |
Baseline
|
|
Virus and host genome
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Collaboratori
Investigatori
- Direttore dello studio: Hong Ren, MM, The Second Affiliated Hospital of Chongqing Medical University
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Infezioni a trasmissione ematica
- Processi patologici
- Malattia cronica
- Attributi della malattia
- Infezioni
- Malattie virali
- Malattie dell'apparato digerente
- Malattie del fegato
- Epatite, virale, umana
- Malattie trasmissibili
- Infezioni da virus del DNA
- Infezioni da Hepadnaviridae
- Epatite cronica
- Epatite
- Condizioni patologiche, segni e sintomi
- Epatite B
- Epatite B, cronica
- Envanfolimab
- Sintilimab
Altri numeri di identificazione dello studio
- 2025-0215
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .