Combination of peg‑IFNα and an anti‑PD‑1 antibody plus antiviral therapy to try to cure chronic hepatitis B

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

This phase 2 test will try adding an anti‑PD‑1 antibody to peg‑IFNα and nucleos(t)ide therapy to see if it produces sustained HBsAg loss in adults with chronic hepatitis B.

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: NCT05771402 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional trial in Chongqing, China tests a sequential combination of nucleos(t)ide analogues (NAs), pegylated interferon‑alpha (peg‑IFNα), and an anti‑PD‑1 antibody to increase rates of sustained HBsAg loss (functional cure). Eligible adults (18–70 years) may be NAs‑naive or NAs‑experienced and must meet weight, BMI, contraception, and safety criteria. The primary outcome is sustained HBsAg loss with close monitoring for antiviral response and immune‑related adverse events during and after treatment. The design builds on prior “New Switch” work that showed improved HBsAg loss when adding interferon to NAs, and now adds PD‑1 blockade to try to further improve cure rates.

Who should consider this trial

Good fit: Adults 18–70 with chronic hepatitis B who meet the study's weight/BMI and contraception requirements and can attend the Chongqing site are the intended candidates.

Not a fit: People with known allergies to the study drugs, recent use of CYP3A4 modulators, recent or ongoing immunosuppression or recent live vaccination, or those unable to attend the trial site are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, the combination could increase the proportion of patients who achieve sustained HBsAg loss and reduce the need for lifelong antiviral therapy.

How similar studies have performed: Previous sequential NA‑to‑interferon protocols (the 'New Switch' program) raised HBsAg loss to about 15% overall and 30–50% in patients with low baseline HBsAg, while adding PD‑1 blockade is a newer approach with limited published clinical results to date.

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; Peg-IFNα