A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (A)
1 other identifier
interventional
120
1 country
1
Brief Summary
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 interferon (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 antibody) 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2023
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 22, 2023
CompletedFirst Posted
Study publicly available on registry
March 15, 2023
CompletedStudy Start
First participant enrolled
October 10, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
September 11, 2025
August 1, 2025
3.2 years
February 22, 2023
September 4, 2025
Conditions
Outcome Measures
Primary Outcomes (12)
Serum HBsAg
Serum HBsAg level
Baseline
Serum HBsAg
Serum HBsAg level
24 weeks after the treatment
Serum HBsAg
Serum HBsAg level
48 weeks after the treatment
Serum HBsAg
Serum HBsAg level
24 weeks after the end of treatment
Serum HBV DNA
Serum HBV DNA level
Baseline
Serum HBV DNA
Serum HBV DNA level
24 weeks after the treatment
Serum HBV DNA
Serum HBV DNA level
48 weeks after the treatment
Serum HBV DNA
Serum HBV DNA level
24 weeks after the end of treatment
Serum alanine aminotransferase (ALT)
Serum ALT level
Baseline
Serum alanine aminotransferase (ALT)
Serum ALT level
24 weeks after the treatment
Serum alanine aminotransferase (ALT)
Serum ALT level
48 weeks after the treatment
Serum alanine aminotransferase (ALT)
Serum ALT level
24 weeks after the end of treatment
Other Outcomes (9)
Other HBV markers
Baseline
Other HBV markers
24 weeks after the treatment
Other HBV markers
48 weeks after the treatment
- +6 more other outcomes
Study Arms (2)
Group 1
EXPERIMENTALNAs combined with anti-PD-1 antibody, followed by NAs monotherapy
Group 2
ACTIVE COMPARATORNAs
Interventions
Once/two or three weeks, dose lower than the dose used in cancer patients, subcutaneous/intravenous injection
Eligibility Criteria
You may qualify if:
- \) 18-70 years old. The weight of male subjects is not less than 45 kg, and the weight of female subjects is not less than 40 kg. Body mass index (BMI) is within the range of 18-32 kg/m\^2;
- \) NAs-naive/NAs-experienced CHB patients.
You may not qualify if:
- \) 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);
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Second Affiliated Hospital of Chongqing Medical Universitylead
- The Affiliated Hospital Of Southwest Medical Universitycollaborator
- Guizhou Provincial People's Hospitalcollaborator
- Chongqing Three Gorges Central Hospitalcollaborator
- First Affiliated Hospital of Chongqing Medical Universitycollaborator
Study Sites (1)
The 2nd affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010, China
Related Publications (1)
He T, Chen M, Liu M, Zhang L, Sun H, Zhang L, Li A, Zeng W, Ling N, Shi X, He H, Peng M, Cai D, Hu P, Zhang D, Lan Y, Ren H. Twenty-four-week anti-PD-1 antibody regimen promoted HBsAg reduction and concurrently enhanced HBV-specific T cell responses in patients with chronic hepatitis B. Gut. 2025 Dec 24:gutjnl-2025-336655. doi: 10.1136/gutjnl-2025-336655. Online ahead of print.
PMID: 41443982DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Hong Ren, MM
The Second Affiliated Hospital of Chongqing Medical University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 22, 2023
First Posted
March 15, 2023
Study Start
October 10, 2023
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
September 11, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share