이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

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).

연구 개요

연구 유형

중재적

등록 (추정된)

1200

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, 중국, 400010
        • 모병
        • The 2nd affiliated Hospital of Chongqing Medical University
        • 수석 연구원:
          • HONG REN, Professor
        • 연락하다:
        • 연락하다:

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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

다른 이름들:
  • Sintilimab(anti-PD-1 antibody)
  • Envafolimab(anti-PD-L1 antibody)

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

활성 비교기: NAs

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

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

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Serum HBsAg
기간: Baseline

Serum HBsAg level

Baseline
Serum HBsAg
기간: 24 weeks after the treatment

Serum HBsAg level

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

Serum HBsAg level

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

Serum HBsAg level

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

Serum HBV DNA level

Baseline
Serum HBV DNA
기간: 24 weeks after the treatment

Serum HBV DNA level

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

Serum HBV DNA level

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

Serum HBV DNA level

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

Serum ALT level

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

Serum ALT level

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

Serum ALT level

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

Serum ALT level

24 weeks after the end of treatment

기타 결과 측정

결과 측정
측정값 설명
기간
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)
기간: Baseline

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

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

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

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

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

Baseline
Virus and host genome
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2023년 10월 10일

기본 완료 (추정된)

2026년 12월 31일

연구 완료 (추정된)

2026년 12월 31일

연구 등록 날짜

최초 제출

2026년 9월 21일

QC 기준을 충족하는 최초 제출

2026년 9월 29일

처음 게시됨 (실제)

2026년 10월 1일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 10월 1일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 29일

마지막으로 확인됨

2026년 9월 1일

추가 정보

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개별 참가자 데이터(IPD) 계획

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아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

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미국 FDA 규제 기기 제품 연구

아니

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