Safety and efficacy of PD-1 antibody combined with pegylated interferon α for functional cure in nucleos(t)ide analogues-suppressed chronic hepatitis B patients: protocol for a multicentre randomised controlled trial.

INTRODUCTION

The functional cure of chronic hepatitis B (CHB) is an ideal goal of therapy, as it is associated with improved long-term outcomes. Patients with low levels of HBsAg have higher rates of functional cure by pegylated interferon α (PEG-IFNα) therapy, and similar results have been observed in patients treated with PD-1 antibody. However, the combination therapy of PD-1 antibody and PEG-IFNα for promoting functional cure has not been studied. This study protocol aims to evaluate the efficacy and safety of a novel combined strategy, PD-1 antibody combined with PEG-IFNα therapy, in nucleos(t)ide analogues (NAs)-treated CHB patients.

METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised controlled study. Virologically suppressed CHB patients by NAs therapy will be recruited and randomised into PEG-IFNα group, PD-1 antibody group or PD-1 antibody combined PEG-IFNα group. PD-1 antibody will be injected intravenously once per 3 weeks for 24 weeks, and PEG-IFNα will be injected subcutaneously once a week for 48 weeks. The primary outcomes are the rate of HBsAg loss at 24 weeks. For safety analysis, adverse events in different groups will be compared.

ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-12-86-3). All results of the study will be submitted to a peer-reviewed journal.

TRIAL REGISTRATION NUMBER: NCT06357806.