Interferon‑based regimens for chronic hepatitis B (CHB) achieve limited efficacy and have notable tolerability issues, making improved patient selection essential to increase rates of functional cure. The GOLDEN model, which relies on sequential measurement of quantitative HBsAg (qHBsAg) kinetics, has demonstrated accurate prediction of HBsAg loss in patients receiving nucleos(t)ide analogue (NA) therapy. However, the model has not been validated in the context of sequential therapy that includes pegylated interferon. This study aims to validate the GOLDEN model and an optimized predictive index (Pi) cut‑off to prospectively identify optimal candidates for clinical cure among NA‑experienced CHB patients who will receive sequential pegylated interferon Peg‑IFN α‑2b based on pre‑IFN qHBsAg dynamics across multiple centres.
This is a prospective multicentre observational cohort study conducted across 22 centres in China. The protocol specifies enrollment of 300 patients with prior exposure to NAs. All enrolled patients will be treated and observed according to the study schedule for the predefined treatment period and endpoints. The multicentre design is intended to evaluate the predictive performance of the GOLDEN model and the selected Pi threshold in a real‑world, geographically diverse clinical population within the participating centres.
Eligible patients are NA‑experienced individuals with chronic hepatitis B. Participants will be stratified before initiation of Peg‑IFN α‑2b based on the predictive index (Pi) calculated from pre‑treatment qHBsAg dynamics. Two strata are defined: a favourable candidate group with Pi > 0.15 (n=150) and an unfavourable candidate group with Pi ≤ 0.15 (n=150). The Pi cut‑off of 0.15 is the prespecified threshold to distinguish predicted higher versus lower likelihood of HBsAg loss based on the GOLDEN framework.
All participants will receive combination therapy consisting of 48 weeks of Peg‑IFN α‑2b administered sequentially with continued background NA therapy. The protocol uses this combination to assess whether patients identified by pre‑treatment qHBsAg kinetics via the GOLDEN model have differential rates of achieving functional cure endpoints during the specified 48‑week treatment period.
The primary endpoint is the HBsAg clearance rate at week 48, defined as loss of HBsAg at any time during the 48‑week treatment period. Secondary endpoints include HBsAg seroconversion and rates of sustained HBsAg clearance. The protocol notes that long‑term follow‑up studies will be required to evaluate durability of clearance and associated clinical outcomes; detailed long‑term follow‑up timing and methods were not reported in the source.
The study will enroll 300 patients, with 150 in each Pi‑stratified group. The sample size provides 80% power to detect a statistically significant difference between the assumed HBsAg clearance rates of 35% in the favourable group versus 20% in the unfavourable group. Between‑group comparisons of categorical endpoints will be performed using chi‑square tests or Fisher’s exact test, as appropriate for the data and cell counts.
Ethical review and approval have been obtained from the ethics committee of Tangdu Hospital, Fourth Military Medical University (approval no. K202509‑69). Approval has also been secured from 21 additional participating centres. The trial is registered under number ChiCTR2500095819. The source did not report additional details such as informed consent procedures, data monitoring arrangements, or safety reporting timelines within this summary.
Concurrently with the primary validation objective, the investigators plan to explore development of novel predictive models using the current framework and other baseline clinical indicators. The protocol indicates a future opportunity to analyse serial inflammatory cytokine profiles from stored blood samples to investigate immunological mechanisms underlying treatment response; the source did not provide specifics regarding which cytokines or the timing of sample collection. The authors also highlight the need for long‑term follow‑up studies to assess sustained HBsAg clearance and its impact on clinical outcomes, without reporting detailed follow‑up schedules in the summary provided.
Trial registration: ChiCTR2500095819. Ethical approval: Tangdu Hospital, Fourth Military Medical University (approval no. K202509‑69); approvals also obtained from 21 additional participating centres.