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

Summary

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.

Timeline

Start

2026-06-01

Primary completion

2028-12-31

Completion

2028-12-31

Publications

• Background Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Guideline for diagnosis and treatment of chronic rhinosinusitis (2024)]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2025 Mar 7;60(3):221-249. doi: 10.3760/cma.j.cn115330-20250116-00051. No abstract available. Chinese.
• Background Shi JB, Fu QL, Zhang H, Cheng L, Wang YJ, Zhu DD, Lv W, Liu SX, Li PZ, Ou CQ, Xu G. Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities. Allergy. 2015 May;70(5):533-9. doi: 10.1111/all.12577. Epub 2015 Mar 4.
• Background Bachert C, Bhattacharyya N, Desrosiers M, Khan AH. Burden of Disease in Chronic Rhinosinusitis with Nasal Polyps. J Asthma Allergy. 2021 Feb 11;14:127-134. doi: 10.2147/JAA.S290424. eCollection 2021.
• Background Stevens WW, Schleimer RP, Kern RC. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016 Jul-Aug;4(4):565-72. doi: 10.1016/j.jaip.2016.04.012.
• Background Zhang L, Zhang Y, Gao Y, Wang K, Lou H, Meng Y, Wang C. Long-term outcomes of different endoscopic sinus surgery in recurrent chronic rhinosinusitis with nasal polyps and asthma. Rhinology. 2020 Apr 1;58(2):126-135. doi: 10.4193/Rhin19.184.
• Background Pelletier A, Endam LM, Gonzalez E, Jannat S, Irani T, Desrosiers M. Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP. Int Forum Allergy Rhinol. 2025 Mar;15(3):227-238. doi: 10.1002/alr.23471. Epub 2024 Oct 23.
• Background Homoe AS, Aanaes K, Tidemandsen JE, Holbaek HC, Niclas R, Badsberg SG, Holmegaard LBI, Backer V. Superior Benefits of Combining Mepolizumab With Sinus Surgery Compared to Mepolizumab Alone: Results From a Randomised 6-Month Trial. Int Forum Allergy Rhinol. 2025 Jul;15(7):724-733. doi: 10.1002/alr.23562. Epub 2025 Mar 10.
• Background Garvey E, Naimi B, Duffy A, Hannikainen P, Kahn C, Farquhar D, Rosen M, Rabinowitz M, Toskala E, Nyquist G. Optimizing the timing of biologic and surgical therapy for patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP). Int Forum Allergy Rhinol. 2024 Mar;14(3):651-659. doi: 10.1002/alr.23246. Epub 2023 Aug 10.
• Background Xian M, Yan B, Song X, Chen J, Tang J, Jiang Y, Wan L, Liu W, Xue J, Cao Z, Yu Y, Yang X, Shi L, Wang G, Xu Y, Yang Y, Ye J, Jiang L, Quan F, Tan G, Liu F, Xu Z, Zhang X, Li J, Su L, Yang Y, Fan J, He G, Zhu L, Wang X, Wang M, Shen S, Li J, Li H, Wei X, Yu H, Liu Z, Ma R, Liu H, Liu J, Lv W, Yang Q, Zhu D, Cheng L, Wang C, Zhang L. Chinese Position Paper on Biologic Therapy for Chronic Rhinosinusitis With Nasal Polyps. Allergy. 2025 May;80(5):1208-1225. doi: 10.1111/all.16519. Epub 2025 Mar 5.
• Background Xian M, Zhang L. Potential of biologics to alter the need for repeated surgery in patients with chronic rhinosinusitis with nasal polyps. Allergy. 2023 Mar;78(3):623-625. doi: 10.1111/all.15565. Epub 2022 Dec 5. No abstract available.
• Background Shen S, Yan B, Wang M, Wu D, Piao Y, Tang J, Yang X, Cao Z, Xue J, Liu W, Liu S, Shi L, Wang G, Song X, Lu Y, Chen J, Jiang L, Ye J, Yu S, Yang Y, Fang H, Li J, Shi H, Fan J, Yan H, Wang H, Chen B, Wang C, Zhang L; CROWNS-2 Study Investigators. Stapokibart for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps: The CROWNS-2 Randomized Clinical Trial. JAMA. 2025 Aug 18;334(11):962-72. doi: 10.1001/jama.2025.12515. Online ahead of print.
• Background Zhang Y, Yan B, Shen S, Song X, Jiang Y, Shi L, Zhao C, Yang Y, Jiang L, Li J, Ye J, Liu J, Wan L, Yang Y, Chen J, Liu F, Su L, Xu Y, Tan G, Yu S, Zhang Y, Wang L, Liu S, Yan H, Liu W, Chen B, Wang C, Zhang L. Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial. EClinicalMedicine. 2023 Jul 5;61:102076. doi: 10.1016/j.eclinm.2023.102076. eCollection 2023 Jul.
• Background Lou H, Meng Y, Piao Y, Wang C, Zhang L, Bachert C. Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population. Am J Rhinol Allergy. 2015 Sep-Oct;29(5):350-6. doi: 10.2500/ajra.2015.29.4231. Epub 2015 Jul 27.
• Background Shah SA, Ishinaga H, Takeuchi K. Pathogenesis of eosinophilic chronic rhinosinusitis. J Inflamm (Lond). 2016 Apr 6;13:11. doi: 10.1186/s12950-016-0121-8. eCollection 2016.
• Background Toppila-Salmi S, Reitsma S, Hox V, Gane S, Eguiluz-Gracia I, Shamji M, Maza-Solano J, Jaaskelainen B, Vaara R, Escribese MM, Chaker A, Karavelia A, Rudenko M, Gevaert P, Klimek L. Endotyping in Chronic Rhinosinusitis-An EAACI Task Force Report. Allergy. 2025 Jan;80(1):132-147. doi: 10.1111/all.16418. Epub 2024 Dec 6.
• Background Bachert C, Hicks A, Gane S, Peters AT, Gevaert P, Nash S, Horowitz JE, Sacks H, Jacob-Nara JA. The interleukin-4/interleukin-13 pathway in type 2 inflammation in chronic rhinosinusitis with nasal polyps. Front Immunol. 2024 Apr 16;15:1356298. doi: 10.3389/fimmu.2024.1356298. eCollection 2024.
• Background Yu J, Xian M, Piao Y, Zhang L, Wang C. Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2-3 Decades. Int Arch Allergy Immunol. 2021;182(7):615-624. doi: 10.1159/000513312. Epub 2021 Feb 17.
• Background Tsuda T, Suzuki M, Kato Y, Kidoguchi M, Kumai T, Fujieda S, Sakashita M. The current findings in eosinophilic chronic rhinosinusitis. Auris Nasus Larynx. 2024 Feb;51(1):51-60. doi: 10.1016/j.anl.2023.08.002. Epub 2023 Aug 11.
• Background Wang M, Wang C, Zhang L. Inflammatory endotypes of CRSwNP and responses to COVID-19. Curr Opin Allergy Clin Immunol. 2021 Feb 1;21(1):8-15. doi: 10.1097/ACI.0000000000000700.
• Background Bhattacharyya N, Villeneuve S, Joish VN, Amand C, Mannent L, Amin N, Rowe P, Maroni J, Eckert L, Yang T, Khan A. Cost burden and resource utilization in patients with chronic rhinosinusitis and nasal polyps. Laryngoscope. 2019 Sep;129(9):1969-1975. doi: 10.1002/lary.27852. Epub 2019 Feb 5.
• Background De Corso E, Bilo MB, Matucci A, Seccia V, Braido F, Gelardi M, Heffler E, Latorre M, Malvezzi L, Pelaia G, Senna G, Castelnuovo P, Canonica GW. Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement. J Pers Med. 2022 May 23;12(5):846. doi: 10.3390/jpm12050846.
• Background Tamene S, Dalhoff K, Schwarz P, Backer V, Aanaes K. Systemic corticosteroids in treatment of chronic rhinosinusitis-A systematic review. Eur Clin Respir J. 2023 Aug 4;10(1):2240511. doi: 10.1080/20018525.2023.2240511. eCollection 2023.
• Background Milara J, Morell A, Ballester B, Armengot M, Morcillo E, Cortijo J. MUC4 impairs the anti-inflammatory effects of corticosteroids in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2017 Mar;139(3):855-862.e13. doi: 10.1016/j.jaci.2016.06.064. Epub 2016 Sep 14.
• Background Bachert C, Marple B, Schlosser RJ, Hopkins C, Schleimer RP, Lambrecht BN, Broker BM, Laidlaw T, Song WJ. Adult chronic rhinosinusitis. Nat Rev Dis Primers. 2020 Oct 29;6(1):86. doi: 10.1038/s41572-020-00218-1.
• Background Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.
• Results Wang W, Kang T, Zhu Z, Wu M, Lv W. Optimal Timing of Dupilumab Application in CRSwNP: Impact of "Neoadjuvant Therapy" on Surgical Outcomes at 1 Year. Int Forum Allergy Rhinol. 2025 Oct;15(10):1175-1177. doi: 10.1002/alr.70014. Epub 2025 Aug 18.

Drugs

Indications