Chronic Hepatitis bPhase 2NCT05769816
A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (A)
A Phase 2 study testing Anti-PD-1 antibody and NAs in people with Chronic Hepatitis b and Anti-PD-1 Antibody, run by The Second Affiliated Hospital of Chongqing Medical University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis b, Anti-PD-1 Antibody
- What is being tested?
- Anti-PD-1 antibody and NAs
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 10 Oct 2023to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) Sign the informed consent form before inclusion and be able to complete the study according to the study requirements;
- 2) From inclusion to 30 days after the last administration of the study drug, male subjects or female subjects of childbearing age are willing to voluntarily take effective contraceptive measures;
- 3) 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;
- 4) NAs-naive/NAs-experienced CHB patients.
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The 2nd affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010
HONG REN, +8613983888786, renhong0531@vip.sina.com
DACHUAN CAI, +8618323409779, cqmucdc@cqmu.edu.cn
About this study
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).
- Conditions
- Chronic Hepatitis b, Anti-PD-1 Antibody
- Being tested
- Anti-PD-1 antibody, NAs
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-PD-1 antibodyDrug
Once/two or three weeks, dose lower than the dose used in cancer patients, subcutaneous/intravenous injection
NAsDrug
Also called ETV/TDF/TAF
Once/day, 1 capsule/time, oral
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | NAs combined with anti-PD-1 antibody, followed by NAs monotherapy Receives: Drug: Anti-PD-1 antibody; Drug: NAs |
| Group 2 | Active comparator | NAs Receives: Drug: NAs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum HBsAg
Serum HBsAg level
Measured: Baseline
Serum HBsAg
Serum HBsAg level
Measured: 24 weeks after the treatment
Serum HBsAg
Serum HBsAg level
Measured: 48 weeks after the treatment
Serum HBsAg
Serum HBsAg level
Measured: 24 weeks after the end of treatment
Serum HBV DNA
Serum HBV DNA level
Measured: Baseline
Serum HBV DNA
Serum HBV DNA level
Measured: 24 weeks after the treatment
Serum HBV DNA
Serum HBV DNA level
Measured: 48 weeks after the treatment
Serum HBV DNA
Serum HBV DNA level
Measured: 24 weeks after the end of treatment
Serum alanine aminotransferase (ALT)
Serum ALT level
Measured: Baseline
Serum alanine aminotransferase (ALT)
Serum ALT level
Measured: 24 weeks after the treatment
Serum alanine aminotransferase (ALT)
Serum ALT level
Measured: 48 weeks after the treatment
Serum alanine aminotransferase (ALT)
Serum ALT level
Measured: 24 weeks after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2023
- Study start10 Oct 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis bStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Second Affiliated Hospital of Chongqing Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- The Affiliated Hospital Of Southwest Medical University, Guizhou Provincial People's Hospital, Chongqing Three Gorges Central Hospital, First Affiliated Hospital of Chongqing Medical University
- Responsible party
- Sponsor
- Investigators
- Hong Ren, MM, Study director, The Second Affiliated Hospital of Chongqing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05769816
- Sponsor's protocol ID
- 2023-0220
- Status last verified
- Sep 2026
- First submitted
- 22 Feb 2023
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. 2026 Jul 8;75(8):1597-1606. doi: 10.1136/gutjnl-2025-336655.
PubMed 41443982