Preoperative Stapokibart for Endoscopic Sinus Surgery in Chronic Rhinosinusitis With Nasal Polyps

Overview

This is a single-center, randomized, double-blinded, placebo-controlled clinical trial in adults with moderate-to-severe chronic rhinosinusitis with nasal polyps (CRSwNP) who have no previous nasal surgery. The purpose of this study is to evaluate the effectiveness and safety of using stapokibart for 4 weeks before endoscopic sinus surgery (ESS), compared with placebo before ESS. The main questions this study aims to answer are: * Does preoperative stapokibart combined with endoscopic sinus surgery achieve better efficacy and comparable safety compared with surgery alone? * What influences four-week preoperative stapokibart administration has on pharmacodynamic data and intraoperative surgical parameters？ * Is there a correlation between the efficacy of four-week stapokibart therapy and postoperative recurrence tendency after endoscopic sinus surgery? Researchers will randomly assign participants to receive either stapokibart or a placebo (an inactive substance that looks like the study drug) for 4 weeks before surgery. All participants will have the same standard endoscopic sinus surgery and will be followed for 48 weeks to check polyp status, symptoms, quality of life, and adverse events. This study will provide evidence about whether short-term preoperative stapokibart improves surgical and long-term outcomes for adults with CRSwNP undergoing ESS.

This is a single-center, randomized, double-blind, placebo-controlled, parallel-group interventional study designed to investigate the clinical value of short-term preoperative use of stapokibart in adult participants with moderate-to-severe chronic rhinosinusitis with nasal polyps (CRSwNP) who are scheduled for primary endoscopic sinus surgery (ESS). Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disorder of the nasal and sinus mucosa characterized by type 2 inflammation, tissue eosinophilia, and frequent disease recurrence despite standard surgical and medical management. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor alpha (IL-4Rα), which blocks the shared signaling pathway of interleukin-4 and interleukin-13, key drivers of type 2 inflammation in CRSwNP. Eligible participants who provide written informed consent will enter a 2-week screening period to confirm compliance with all enrollment criteria. Eligible participants will be randomized 1:1 using a stratified block randomization approach (stratified by asthma comorbidity) to receive either stapokibart 300 mg or placebo via subcutaneous injection every two weeks for a total of two doses. All participants, investigators, outcome assessors, and study personnel remain blinded to treatment assignment throughout the study to minimize assessment bias. Endoscopic sinus surgery will be performed two weeks after the second study drug injection (four weeks after the first injection) using a standardized bilateral full-house sinus opening technique under general anesthesia.Intraoperative data including operative duration, estimated blood loss, and surgical field visualization quality are prospectively recorded. All participants will receive uniform postoperative care consisting of intranasal corticosteroids and nasal irrigation according to standard clinical practice. Participants will be followed for up to 48 weeks after surgery, with scheduled assessments at 2, 4, 12, 24, 36, and 48 weeks postoperatively. Throughout the entire study period, all participants receive routine maintenance treatment with nasal corticosteroid spray. During the study, serial clinical evaluations will be conducted, and biomaterial samples will be collected at baseline and during surgery to explore changes in local inflammatory markers, inflammatory cell infiltration, vascular endothelial activation, and epithelial tight junction protein expression. These exploratory analyses aim to clarify the mechanisms by which stapokibart modulates mucosal inflammation in the perioperative setting. Safety monitoring will be conducted throughout the study, including documentation of all adverse events, serious adverse events, and clinically significant changes in vital signs or laboratory parameters. The study design incorporates strict rules for rescue therapy, including systemic corticosteroids, additional biologic therapy, or repeat surgery, which will be recorded as study endpoints. Statistical analyses will be performed using predefined analysis populations, including the Full Analysis Set (FAS) population and safety analysis set. The primary analysis will evaluate differences between treatment groups in the primary efficacy endpoint, with appropriate handling of missing data and adjustment for baseline covariates and stratification factors. This study is designed to generate high-quality clinical evidence regarding the efficacy and safety of preoperative short-course stapokibart as a perioperative intervention, with the goal of supporting optimized, personalized, and cost-effective integrated management strategies for adults with moderate-to-severe CRSwNP undergoing primary endoscopic sinus surgery.