TY  - JOUR
PB  - American Society of Nephrology
N1  - This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/).
TI  - Developing Therapies for C3 Glomerulopathy: Report of the Kidney Health Initiative C3 Glomerulopathy Trial Endpoints Work Group
Y1  - 2024/09//
A1  - Nester, Carla
A1  - Decker, Dima A
A1  - Meier, Matthias
A1  - Aslam, Shakil
A1  - Bomback, Andrew S
A1  - Caravaca-Fontán, Fernando
A1  - Cook, Terence H
A1  - Feldman, David L
A1  - Fremeaux-Bacchi, Veronique
A1  - Gale, Daniel P
A1  - Gooch, Ann
A1  - Johnson, Sally
A1  - Licht, Christoph
A1  - Mathur, Mohit
A1  - Pickering, Matthew C
A1  - Praga, Manuel
A1  - Remuzzi, Giuseppe
A1  - Selvarajah, Viknesh
A1  - Smith, Richard J
A1  - Tabriziani, Hossein
A1  - Van de Kar, Nicole
A1  - Wang, Yaqin
A1  - Wong, Edwin
A1  - Mistry, Kirtida
A1  - Lim, Mark
A1  - Portillo, Cesia
A1  - Balogun, Seyi
A1  - Trachtman, Howard
A1  - Thompson, Aliza
VL  - 19
UR  - http://dx.doi.org/10.2215/cjn.0000000000000505
N2  - Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3G, a rare glomerular disease. The Kidney Health Initiative (KHI) convened a panel of experts in C3G to: (1) assess the data supporting the use of the prespecified trial endpoints as measures of clinical benefit; and (2) opine on efficacy findings they would consider compelling as treatment(s) for 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 endpoints -- (1) proteinuria; (2) estimated glomerular filtration rate (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 endpoints 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, the evidence, and uncertainties, supporting the endpoints. Given the limitations of the available data, the workgroup was unable to define a minimum threshold for change in any of the endpoints that might be considered clinically meaningful. The workgroup concluded that a favorable treatment effect on all three endpoints 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 endpoints 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 endpoints in the aforementioned trials.
EP  - 1208
ID  - discovery10194182
SP  - 1201
SN  - 1555-9041
JF  - Clinical Journal of the American Society of Nephrology
AV  - public
IS  - 9
ER  -