Anti‑PD‑1 plus antivirals and interferon to try for sustained HBsAg loss in chronic hepatitis B

A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (A)

This trial will try adding an anti‑PD‑1 antibody to standard nucleos(t)ide antivirals (with sequential interferon in some patients) to see if more adults with chronic hepatitis B can achieve sustained HBsAg loss.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: The Second Affiliated Hospital of Chongqing Medical University (Academic / other)
• Locations: 1 site (Chongqing, Chongqing Municipality)
• Trial ID: NCT05769816 on ClinicalTrials.gov

What this trial studies

This Phase 2 trial tests a combination approach that adds an anti‑PD‑1 antibody to ongoing nucleos(t)ide analogue (NA) therapy and uses sequential interferon in some patients to pursue sustained HBsAg loss (functional cure). It enrolls adults 18–70 years old, including both NA‑naive and NA‑experienced patients, with standard BMI and contraception requirements. The design builds on a prior 'New Switch' program that increased HBsAg loss to about 15% overall and 30–50% in patients with lower baseline HBsAg by adding interferon after NA therapy. The study aims to see whether adding PD‑1 blockade can further raise durable HBsAg loss rates while monitoring safety.

Who should consider this trial

Good fit: Adults aged 18–70 with chronic hepatitis B who meet BMI and contraception requirements and who are either NA‑naive or NA‑experienced may be eligible.

Not a fit: Patients with recent use of immunosuppressants or certain CYP3A4 interacting drugs, known allergy to the study agents, or other exclusionary conditions are unlikely to be eligible and may not receive benefit.

Why it matters

Potential benefit: If successful, this combination approach could substantially increase the proportion of patients who achieve sustained HBsAg loss and lower long‑term liver disease risk.

How similar studies have performed: Previous sequential NA-to‑interferon 'New Switch' work increased HBsAg loss rates moderately, but adding PD‑1 blockade in chronic HBV is relatively novel and not yet proven effective.

Eligibility criteria

Inclusion Criteria:

* 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.

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

Where this trial is running

Chongqing, Chongqing Municipality

• The 2nd affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Dachuan Cai, MD

Conditions Chronic Hepatitis b; Anti-PD-1 Antibody