Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy
Jonathan Barratt, Richard Lafayette, Jens Kristensen, Andrew Stone, Daniel Cattran, Jürgen Floege, Vladimı́r Tesař, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Brad H. Rovin, Guillermo Fragale, Alejandra Karl, Patricia Losisolo, Hernán Trimarchi, Ivan Gonzalez Hoyos, Mauro Lampo, Matías Monkowski, Jorge de la Fuente, Magdalena Alvarez, Daniela Stoppa, Carlos Chiurchiu, P. Novoa, Marcelo Orías, Maria Belen Barron, Ana Paula Giotto, M. Arriola, Evelin Cassini, Rafaël Maldonado, Maria Paula Dionisi, Jessica Ryan, Nigel D. Toussaint, Grant Luxton, Chen Au Peh, Vicki Levidiotis, Ross S. Francis, Richard Phoon, Elena Fedosiuk, D.M. Toropilov Toropilov, R. E. Yakubtsevich, Elena Mikhailova, Christophe Bovy, Nathalie Demoulin, Jean‐Michel Hougardy, Bart Maes, Marijn M. Speeckaert, Louis‐Philippe Laurin, Sean Barbour, Mélanie Masse, Michelle Hladunewich, Heather N. Reich, Serge Cournoyer, Karthik Tennankore, Sean Barbour, Jicheng Lv, Zhangsuo Liu, Caili Wang, Shaomei Li, Qun Luo, Zhaohui Ni, Tiekun Yan, Ping Fu, Hong Cheng, Bi‐Cheng Liu, Wanhong Lu, Jianqin Wang, Qinkai Chen, D. Wang, Zuying Xiong, Menghua Chen, Yan Xu, Jiali Wei, Pearl Pai, Lianhua Chen, Jitka Řehořová, Dita Maixnerová, Roman Šafránek, Ivan Rychlík, M Hrubý, Satu Mäkelä, Kati Vääräniemi, Fernanda Ortiz, É. Alamartine, Maïté Daroux, C. Cartery, François Vrtovsnik, Jean‐Emmanuel Serre, Eleni Stamellou, Volker Vielhauer, Christian Hugo, Klemens Budde, Britta Otte, Martin Nitschke, Evangelia Ntounousi, Ioannis Boletis, Αikaterini Papagianni, Dimitrios Goumenos, Kostas Stylianou, Synodi Zermpala
Abstract
The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m 2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study.