Evaluating a New Combination Therapy of Immune Checkpoint Inhibitors and Peg-IFNb1 with Nucleostide Analogues for Functional Cure in Chronic Hepatitis B

What This Trial Is About

Chronic Hepatitis B virus HBV infection poses a significant public health challenge in China. Achieving a functional cure, defined as sustained loss of Hepatitis B surface antigen HBsAg, remains difficult with current antiviral treatments, with less than 10% success using interferon IFNb1 or nucleostide analogues NAs alone. Building on a previous study that improved the HBsAg loss rate to 15%, this trial explores an innovative combination therapy aimed at enhancing immune response to increase cure rates. Participants will receive one of two treatments either a combination of NAs, anti-PD-1anti-PD-L1 antibodies immune checkpoint inhibitors, and Peg-IFNb1, or a combination of NAs and Peg-IFNb1 alone. The anti-PD-1PD-L1 antibody is administered subcutaneously or intravenously every one to three weeks at doses lower than those used in cancer therapy. NAs are taken orally once daily, and Peg-IFNb1 is given as a weekly subcutaneous injection. This large multicenter Phase 2 study aims to assess the safety and effectiveness of these regimens in improving the clinical cure rate by reversing T cell exhaustion. During the study, participants will be monitored through blood tests measuring HBsAg, HBV DNA, and liver enzyme levels at baseline, 24 weeks, 48 weeks post-treatment, and 24 weeks after treatment ends. Regular assessments will evaluate immune response and viral control. The study intends to increase the HBsAg loss rate beyond 50% and contribute to global HBV elimination goals. Total participation duration aligns with treatment and follow-up assessments over approximately one year.

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