A Randomized, Placebo-Controlled, Double-Blinded Trial of Preoperative Stapokibart With Endoscopic Sinus Surgery for Chronic Rhinosinusitis With Nasal Polyps
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Possess the ability to understand the nature of the study and voluntarily sign an informed consent form (ICF);
- •Age between 18 and 75 years old, with no limitation on gender;
- •Bilateral CRSwNP meeting the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Chronic Sinusitis (2024);
- •Persistent presence of the following symptoms for ≥12 weeks prior to the screening/introduction period:
- •Nasal congestion;
- •Any other symptom such as decreased/loss of smell or rhinorrhea;
- •At the screening/introduction period and baseline, total NPS ≥ 4 points and NPS ≥ 2 points in each nasal cavity;
- •At the screening/introduction period and baseline, the subject reports moderate to severe nasal congestion or decreased smell (NCS or LoS score of 2 or 3 points);
- •During the screening/introduction period, the Lund-Mackay score on sinus CT is ≥12 points bilaterally and ≥6 points unilaterally;
- •Must meet any of the following criteria for type 2 inflammation: Eosinophil count >55/high-power field or eosinophil percentage >27% in nasal polyp tissue during the induction period; eosinophil percentage ≥3.75% in peripheral blood in patients with asthma; eosinophil percentage ≥6.9% in patients without asthma;
- •If the subject has asthma, the condition must be stable as assessed by the investigator or specialist. For subjects treated with a stable dose of inhaled corticosteroids for at least 4 weeks before screening, the treatment may be continued during the study period, and the daily dose of inhaled corticosteroids must be ≤1000 μg fluticasone propionate or an equivalent dose of other inhaled corticosteroids.
排除标准
- •Previous ESS surgery including but not limited to septoplasty, turbinate reduction, nasal polyp removal, and sinus surgery;
- •Contraindications to general anesthesia;
- •Contraindications to stapokibart therapy;
- •Previous use of any anti-IL-4Rα biologic;
- •The patient has conditions or comorbidities that may prevent them from being evaluated for the primary efficacy endpoint, such as acute rhinitis, nasal infection or upper respiratory tract infection within 2 weeks prior to the screening period, acute asthma exacerbation within 4 weeks, current drug-induced rhinitis, allergic fungal sinusitis (AFRS), benign or malignant nasal tumors;
- •Important clinical comorbidities that may interfere with clinical efficacy results, including but not limited to active upper or lower respiratory tract infection, cystic fibrosis, eosinophilic granuloma with polyangiitis (Churg-Strauss syndrome), granuloma with polyangiitis (Wegener's granulomatosis), Young's syndrome, etc.;
- •Accompanied by other poorly controlled serious diseases or recurrent chronic diseases such as (but not limited to) active infection, cardiovascular disease, tuberculosis or other pathogen infection, diabetes, autoimmune diseases, HIV, hepatitis B, hepatitis C or parasitic diseases, malignant tumors, etc.;
- •Subjects with severe liver or kidney dysfunction, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 2 times the upper limit of normal, and serum creatinine > the upper limit of normal;
- •Subjects with known or suspected immunosuppression, including those with a history of invasive opportunistic infections (such as tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pulmonary cystitis, aspergillosis), even if the infection has subsided;
- •Women who are pregnant or planning to become pregnant during the study period, or who are breastfeeding;
- •Subjects of childbearing age who do not wish to use medically approved effective contraception;
- •Subjects with a history of alcohol or drug abuse;
- •Subjects deemed by the investigator to have other medical or non-medical conditions that make them unsuitable for participation in this study.
研究者
Mu Xian
Chief Physician, Professor
Beijing Tongren Hospital