Carla Nester, Dima A Decker, Matthias Meier, Shakil Aslam, Andrew S Bomback, Fernando Caravaca-Fontán, Terence H Cook, David L Feldman, Veronique Fremeaux-Bacchi, Daniel P Gale, Ann Gooch, Sally Johnson, Christoph Licht, Mohit Mathur, Matthew C Pickering, Manuel Praga, Giuseppe Remuzzi, Viknesh Selvarajah, Richard J Smith, Hossein Tabriziani, Nicole van de Kar, Yaqin Wang, Edwin Wong, Kirtida Mistry, Mark Lim, Cesia Portillo, Seyi Balogun, Howard Trachtman, Aliza Thompson
{"title":"Developing Therapies for C3 Glomerulopathy: Report of the Kidney Health Initiative C3 Glomerulopathy Trial Endpoints Work Group.","authors":"Carla Nester, Dima A Decker, Matthias Meier, Shakil Aslam, Andrew S Bomback, Fernando Caravaca-Fontán, Terence H Cook, David L Feldman, Veronique Fremeaux-Bacchi, Daniel P Gale, Ann Gooch, Sally Johnson, Christoph Licht, Mohit Mathur, Matthew C Pickering, Manuel Praga, Giuseppe Remuzzi, Viknesh Selvarajah, Richard J Smith, Hossein Tabriziani, Nicole van de Kar, Yaqin Wang, Edwin Wong, Kirtida Mistry, Mark Lim, Cesia Portillo, Seyi Balogun, Howard Trachtman, Aliza Thompson","doi":"10.2215/CJN.0000000000000505","DOIUrl":null,"url":null,"abstract":"<p><p>Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3 glomerulopathy (C3G), a rare glomerular disease. The Kidney Health Initiative convened a panel of experts in C3G to ( 1 ) assess the data supporting the use of the prespecified trial end points as measures of clinical benefit and ( 2 ) opine on efficacy findings they would consider compelling as treatment(s) of C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work Group reviewed the available evidence and uncertainties for the association between the three prespecified end points-( 1 ) proteinuria, ( 2 ) eGFR, and ( 3 ) histopathology-and anticipated outcomes. The full work group provided feedback on the summaries provided by the subpanels and on what potential treatment effects on the proposed end points they would consider compelling to support evidence of an investigational product's effectiveness for treating C3G. Members of the full work group agreed with the characterization of the data, evidence, and uncertainties, supporting the end points. Given the limitations of the available data, the work group was unable to define a minimum threshold for change in any of the end points that might be considered clinically meaningful. The work group concluded that a favorable treatment effect on all three end points would provide convincing evidence of efficacy in the setting of a therapy that targeted the complement pathway. A therapy might be considered effective in the absence of complete alignment in all three end points if there was meaningful lowering of proteinuria and stabilization or improvement in eGFR. The panel unanimously supported efforts to foster data sharing between academic and industry partners to address the gaps in the current knowledge identified by the review of the end points in the aforementioned trials.</p>","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":8.5000,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Journal of the American Society of Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2215/CJN.0000000000000505","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3 glomerulopathy (C3G), a rare glomerular disease. The Kidney Health Initiative convened a panel of experts in C3G to ( 1 ) assess the data supporting the use of the prespecified trial end points as measures of clinical benefit and ( 2 ) opine on efficacy findings they would consider compelling as treatment(s) of C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work Group reviewed the available evidence and uncertainties for the association between the three prespecified end points-( 1 ) proteinuria, ( 2 ) eGFR, and ( 3 ) histopathology-and anticipated outcomes. The full work group provided feedback on the summaries provided by the subpanels and on what potential treatment effects on the proposed end points they would consider compelling to support evidence of an investigational product's effectiveness for treating C3G. Members of the full work group agreed with the characterization of the data, evidence, and uncertainties, supporting the end points. Given the limitations of the available data, the work group was unable to define a minimum threshold for change in any of the end points that might be considered clinically meaningful. The work group concluded that a favorable treatment effect on all three end points would provide convincing evidence of efficacy in the setting of a therapy that targeted the complement pathway. A therapy might be considered effective in the absence of complete alignment in all three end points if there was meaningful lowering of proteinuria and stabilization or improvement in eGFR. The panel unanimously supported efforts to foster data sharing between academic and industry partners to address the gaps in the current knowledge identified by the review of the end points in the aforementioned trials.
期刊介绍:
The Clinical Journal of the American Society of Nephrology strives to establish itself as the foremost authority in communicating and influencing advances in clinical nephrology by (1) swiftly and effectively disseminating pivotal developments in clinical and translational research in nephrology, encompassing innovations in research methods and care delivery; (2) providing context for these advances in relation to future research directions and patient care; and (3) becoming a key voice on issues with potential implications for the clinical practice of nephrology, particularly within the United States. Original manuscript topics cover a range of areas, including Acid/Base and Electrolyte Disorders, Acute Kidney Injury and ICU Nephrology, Chronic Kidney Disease, Clinical Nephrology, Cystic Kidney Disease, Diabetes and the Kidney, Genetics, Geriatric and Palliative Nephrology, Glomerular and Tubulointerstitial Diseases, Hypertension, Maintenance Dialysis, Mineral Metabolism, Nephrolithiasis, and Transplantation.