Oral iptacopan therapy in patients with C3 glomerulopathy: a randomised, double-blind, parallel group, multicentre, placebo-controlled, phase 3 study

作者：David Kavanagh, David Kavanagh, Andrew S Bomback, Marina Vivarelli, Carla M Nester, Giuseppe Remuzzi, Ming-Hui Zhao, Yaqin Wang, Yaqin Wang, Induja Krishnan, Imelda Schuhmann, Angelo J. Trapani, Nicholas J.A. Webb, Matthias Meier, Rubeen K Israni, Richard J H Smith, A Ramos Espinosa, Rita Marcela Fortunato, Magali Freijo Freijo, Nadia Viviana Fretes, Pablo Raffaele, Gianna Mastroianni Kirsztajn, Juliana Mansur Siliano, Laila Almeida Viana, Dervla M. Connaughton, Susan Huang, Faisal Rehman, Pavel Roshanav, M. Lynn Weir, Dong-Yuan Chang, Pei Chen, Bixia Gao, Ying Tan, Li Yang, Xiaojuan Yu, Xin Zhang, Chuan‐Ming Hao, Chuan‐Ming Hao, Lingyun Lai, Shaojun Liu, Eva Jančová, Vladimı́r Tesař, Anne Blanchard, Sophie Chauvet, Nathalie Chavarot, Roxane Gaïsset, François Provôt, Myriam Dao, Hamza Sakhi, Aude Servais, Julia Weinmann‐Menke, Ute Eisenberger, Anja Gäckler, Benjamin Wilde, Anne Dieterle, Michael S. Wiesener, Tobias B. Huber, Malte A. Kluger, Eleftheria‐Kleio Dermitzaki, Charikleia Gakiopoulou, Konstantinos Stylianou, Narayan Prasad, Dharmendra Bhadauria, Dinesh Khullar, Soumita Bagchi, Naomi Ben-Dor, Valeria Morduhovich, Benaya Rozen‐Zvi, Yael Borovitz, Daniel Landau, Camillo Carrara, Erica Daina, Amantia Imeraj, Maddalena Marasà, Piero Ruggenenti, Giuseppe Remuzzi, Luca Antonucci, Marcello Chinali, Antonio Gargiulo, Marina Vivarelli, Federica Zotta, Sosuke Fukui, Hangsoo Kim, Masashi Mizuno, Yasuhíro Suzuki, Shin Goto, Michihiro Hosojima, Hideyuki Kabasawa, Yoshikatsu Kaneko, Ryohie Kaseda, Ichiei Narita, Tadashi Otsuka, Hirofumi Watanabe, Suguru Yamamoto, Motoki Matsuki, Naoki Nagakawa, Wataru Ohwada, Arata Osanami, Hidemichi Kouzu, Tomohisa Yamashita, Toshiyuki Yano, Hanneke Bouwsma, Aiko Popke Jan de Vries, Soufiane Meziyerh, W. T. Moest, Dennis A. J. van den Broek, Y.K. Onno Teng, Teresa Cavero Escribano, Wenceslao Adrian Aguilera Morales, Francisco José de la Prada Álvarez, Fabiola Alonso García, Mercedes Salgueira Lazo, Katarina Benackova, Uyen Huynh‐Do, Laila‐Yasmin Mani, Sibylle Tschumi, Asil Demirezen, Özant Helvacı, Betül Öğüt, Saliha Yıldırım, David Kavanagh, David Kavanagh, Edwin Wong, Tom Cairns, Stephen P. McAdoo, Liz Lightstone, Nicholas Medjeral‐Thomas, Matthew C. Pickering, Wooin Ahn, Gerald B. Appel, Andrew S. Bomback, Pietro A. Canetta, Elizabeth Hendren, Allyson Medina, Mariela Navarro-Torress, Jai Radhakrishnan, Jennifer G. Jetton, Christina J. Michels, Carla M. Nester, Richard J. Smith, James A. Tumlin · 发表于：The Lancet · 年份：2025 · DOI：10.1016/s0140-6736(25)01148-1 · 被引用次数：47 · 研究领域：Complement system in diseases、Mechanical Circulatory Support Devices、Peripheral Neuropathies and Disorders

Background C3 glomerulopathy is an ultra-rare, severe form of glomerulonephritis caused by overactivation of the alternative complement pathway. We aimed to assess efficacy and safety of iptacopan (LNP023), an oral, proximal complement inhibitor that targets factor B to selectively inhibit the alternative pathway of the complement cascade. Methods APPEAR-C3G was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study of iptacopan versus placebo (both in addition to supportive care [renin–angiotensin–aldosterone system (RAAS) inhibitors] and immunosuppression). Adult participants (aged 18–60 years) with biopsy-confirmed C3 glomerulopathy were enrolled from 35 hospitals or medical centres in 18 countries. Inclusion criteria included reduced serum C3 concentration (ie, <77 mg/dL [defined as <0·85 × lower limit of the central laboratory normal range]) at screening, urine protein–creatinine ratio (UPCR) of 1·0 g/g or higher at day –75 and day –15 before randomisation, estimated glomerular filtration rate (eGFR) of 30 mL/min per 1·73 m 2 or higher at screening and day –15, and vaccination against Neisseria meningitidis and Streptococcus pneumoniae . All eligible participants were randomised 1:1 via interactive response technology to either the iptacopan or the placebo group, stratified by treatment with corticosteroids, mycophenolic acid, or both (yes or no). During the 6-month double-blind period, participants orally received either iptacopan 200 mg twice daily ...