Evaluation of the Efficacy and Safety of a PD-1 Inhibitor Combined with Peg-IFN in Patients with Chronic Hepatitis B: A Protocol for a Prospective Nonrandomized Controlled Trial

Background In adult chronic hepatitis B (CHB) patients with a favorable response to interferon therapy, an hepatitis B surface antigen (HBsAg) clearance rate exceeding 40% can be achieved. However, for the remaining population, which constitutes more than half of the HBsAg non-clearance cases, effective clinical cure options are still lacking. Therefore, in this non-randomized controlled trial, we aim to evaluate the efficacy and safety of sequential combination therapy with a programmed death receptor 1 (PD-1) inhibitor in patients who have not achieved HBsAg clearance after 48 weeks of pegylated interferon alpha (Peg-IFNα) treatment. Methods This study is a nonrandomized controlled trial. Patients with chronic hepatitis B who received Peg-IFNα treatment for 48 weeks but without HBsAg clearance were enrolled. Participants were divided into two groups on the basis of their treatment willingness. The treatment group will receive combined therapy with a PD-1 inhibitor and Peg-IFNα, whereas the Peg-IFNα regimen will be continued in the control group. All patients will also receive nucleos(t)ide analogs (NAs) antiviral therapy. Follow-up assessments will be conducted at baseline and at weeks 4, 12, and 24 to evaluate the difference in HBsAg clearance rates between the two groups and to assess the safety of a PD-1 inhibitor combined with Peg-IFNα therapy in the treatment group. The primary endpoint will be the HBsAg clearance rate at week 24. Discussion This clinical trial will elucidate the efficacy and safety of PD-1 inhibitors combined with Peg-IFNα in clearing HBsAg in CHB patients who have not been cured by interferon. Trial registration www.chictr.org.cn. Identifier: ChiCTR2400091948, Registered on 6 November 2024.