Sequential PD-1 Antibody and Pegylated Interferon Therapy for Nucleos(t)Ide Analogue-suppressed Chronic Hepatitis B

Safety and Efficacy of Sequential Treatment With a PD-1 Antibody and Pegylated Interferon-α in Nucleos(t)Ide Analogue-Suppressed Patients With Chronic Hepatitis B

This is a prospective, multicenter, randomized, open-label controlled clinical trial designed to evaluate the efficacy and safety of a sequential treatment strategy incorporating a PD-1 antibody and pegylated interferon-α (Peg-IFNα) in patients with chronic hepatitis B receiving stable nucleos(t)ide analogue (NA) therapy.

A total of 60 participants will be randomly assigned in a 1:1 ratio to an experimental group or a control group. Participants in the experimental group will initially receive a PD-1 antibody in combination with continued NA therapy, followed by a period of triple therapy with the PD-1 antibody, Peg-IFNα, and NAs. The PD-1 antibody will then be discontinued, while Peg-IFNα plus NAs will be continued through Week 48. Participants in the control group will receive Peg-IFNα plus continued NA therapy from baseline through Week 48.

Inclusion Criteria:

• 1. Aged 18-55 years;
• 2.Chronic hepatitis B patients with clear diagnosis of hematology, etiology and clinical (for example: HBsAg positive for more than 6 months);
• 3. Treatment with NAs(ETV, TDF or TAF)at least 1 years and continue NAs therapy during screening;
• 4.Patients with HBV DNA negative, HBeAg negative, HBsAg quantification ≤ 500IU/ml .

Exclusion Criteria:

• 1. Cirrhosis;
• 2.platelet count < 90×10^9/L, WBC count < 3.0×10^9/L, ALT /AST> ULN (40U/L), total bilirubin > 2ULN;
• 3.History of or suspicion of hepatocellular carcinoma
• 4.Patients received interferon therapy within 6 months;
• 5.Patients received immunosuppressive therapy or other therapy influenced study within 6 months;
• 6.Pregnancy
• 7.Hepatitis A, hepatitis C, hepatitis D, HIV infection or other active infections;
• 8.Presence of severe uncontrolled diseases of respiratory, cardiovascular or other organ systems;
• 9.Alcohol or drug abuse/dependence;
• 10.Other conditions rendering subjects ineligible for enrollment, including but not limited to absolute contraindications to interferon therapy, known hypersensitivity to any study drug or their excipients, and anticipated poor compliance with treatment and follow-up procedures.