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, Vladimir Tesar, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Brad H Rovin, NefIgArd Trial Investigators, Guillermo Fragale, Alejandra Karl, Patricia Losisolo, Hernán Trimarchi, Ivan Gonzalez Hoyos, Mauro Guillermo Lampo, Matias Monkowski, Jorge De La Fuente, Magdalena Alvarez, Daniela Stoppa, Carlos Chiurchiu, Pablo Antonio Novoa, Marcelo Orias, Maria Belen Barron, Ana Giotto, Mariano Arriola, Evelin Cassini, Rafael Maldonado, Maria Paula Dionisi, Jessica Ryan, Nigel Toussaint, Grant Luxton, Chen Au Peh, Vicki Levidiotis, Ross Francis, Richard Phoon, Elena Fedosiuk, Dmitry Toropilov, Ruslan Yakubtsevich, Elena Mikhailova, Christophe Bovy, Nathalie Demoulin, Jean-Michel Hougardy, Bart Maes, Marijn Speeckaert, Louis-Philippe Laurin, Sean Barbour, Melanie Masse, Michelle Hladunewich, Heather 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, Bicheng Liu, Wanhong Lu, Jianqin Wang, Qinkai Chen, DeGuang Wang, Zuying Xiong, Menghua Chen, Yan Xu, Jiali Wei, Pearl Pai, Lianhua Chen, Jitka Rehorova, Dita Maixnerova, Roman Safranek, Ivan Rychlik, Miroslav Hruby, Satu Makela, Kati Vaaraniemi, Fernanda Ortiz, Eric Alamartine, Maite Daroux, Claire Cartery, Francois Vrtovsnik, Jean-Emmanuel Serre, Eleni Stamellou, Volker Vielhauer, Christian Hugo, Klemens Budde, Britta Otte, Martin Nitschke, Evangelia Ntounousi, Ioannis Boletis, Aikaterini Papagianni, Dimitrios Goumenos, Konstantinos Stylianou, Synodi Zermpala, Ciro Esposito, Mario Gennaro Cozzolino, Sara Maria Viganò, Loreto Gesualdo, Michal Nowicki, Tomasz Stompor, Ilona Kurnatowska, Sung Gyun Kim, Yong-Lim Kim, Ki-Ryang Na, Dong Ki Kim, Su-Hyun Kim, Luis Quintana Porras, Eva Rodriguez Garcia, Irene Agraz Pamplona, Alfons Segarra, Marian Goicoechea, Bengt Fellstrom, Sigrid Lundberg, Peter Hemmingsson, Gregor Guron, Anna Sandell, Cheng-Hsu Chen, Bulent Tokgoz, Soner Duman, Mehmet Riza Altiparmak, Metin Ergul, Peter Maxwell, Patrick Mark, Kieran McCafferty, Arif Khwaja, Chee Kay Cheung, Matthew Hall, Albert Power, Durga Kanigicherla, Richard Baker, Jim Moriarty, Amr Mohamed, Joseph Aiello, Pietro Canetta, Isabelle Ayoub, Derrick Robinson, Surabhi Thakar, Amy Mottl, Isaac Sachmechi, Bernard Fischbach, Harmeet Singh, Jeffrey Mulhern, Fahmeedah Kamal, Douglas Linfert, Dana Rizk, Shikha Wadhwani, Menaka Sarav, Kirk Campbell, Gaia Coppock, Randy Luciano, John Sedor, Rupali Avasare, Wai Lang Lau, Jonathan Barratt, Richard Lafayette, Jens Kristensen, Andrew Stone, Daniel Cattran, Jürgen Floege, Vladimir Tesar, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Brad H Rovin, NefIgArd Trial Investigators, Guillermo Fragale, Alejandra Karl, Patricia Losisolo, Hernán Trimarchi, Ivan Gonzalez Hoyos, Mauro Guillermo Lampo, Matias Monkowski, Jorge De La Fuente, Magdalena Alvarez, Daniela Stoppa, Carlos Chiurchiu, Pablo Antonio Novoa, Marcelo Orias, Maria Belen Barron, Ana Giotto, Mariano Arriola, Evelin Cassini, Rafael Maldonado, Maria Paula Dionisi, Jessica Ryan, Nigel Toussaint, Grant Luxton, Chen Au Peh, Vicki Levidiotis, Ross Francis, Richard Phoon, Elena Fedosiuk, Dmitry Toropilov, Ruslan Yakubtsevich, Elena Mikhailova, Christophe Bovy, Nathalie Demoulin, Jean-Michel Hougardy, Bart Maes, Marijn Speeckaert, Louis-Philippe Laurin, Sean Barbour, Melanie Masse, Michelle Hladunewich, Heather 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, Bicheng Liu, Wanhong Lu, Jianqin Wang, Qinkai Chen, DeGuang Wang, Zuying Xiong, Menghua Chen, Yan Xu, Jiali Wei, Pearl Pai, Lianhua Chen, Jitka Rehorova, Dita Maixnerova, Roman Safranek, Ivan Rychlik, Miroslav Hruby, Satu Makela, Kati Vaaraniemi, Fernanda Ortiz, Eric Alamartine, Maite Daroux, Claire Cartery, Francois Vrtovsnik, Jean-Emmanuel Serre, Eleni Stamellou, Volker Vielhauer, Christian Hugo, Klemens Budde, Britta Otte, Martin Nitschke, Evangelia Ntounousi, Ioannis Boletis, Aikaterini Papagianni, Dimitrios Goumenos, Konstantinos Stylianou, Synodi Zermpala, Ciro Esposito, Mario Gennaro Cozzolino, Sara Maria Viganò, Loreto Gesualdo, Michal Nowicki, Tomasz Stompor, Ilona Kurnatowska, Sung Gyun Kim, Yong-Lim Kim, Ki-Ryang Na, Dong Ki Kim, Su-Hyun Kim, Luis Quintana Porras, Eva Rodriguez Garcia, Irene Agraz Pamplona, Alfons Segarra, Marian Goicoechea, Bengt Fellstrom, Sigrid Lundberg, Peter Hemmingsson, Gregor Guron, Anna Sandell, Cheng-Hsu Chen, Bulent Tokgoz, Soner Duman, Mehmet Riza Altiparmak, Metin Ergul, Peter Maxwell, Patrick Mark, Kieran McCafferty, Arif Khwaja, Chee Kay Cheung, Matthew Hall, Albert Power, Durga Kanigicherla, Richard Baker, Jim Moriarty, Amr Mohamed, Joseph Aiello, Pietro Canetta, Isabelle Ayoub, Derrick Robinson, Surabhi Thakar, Amy Mottl, Isaac Sachmechi, Bernard Fischbach, Harmeet Singh, Jeffrey Mulhern, Fahmeedah Kamal, Douglas Linfert, Dana Rizk, Shikha Wadhwani, Menaka Sarav, Kirk Campbell, Gaia Coppock, Randy Luciano, John Sedor, Rupali Avasare, Wai Lang Lau
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 m2 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.
Keywords: IgA nephropathy; glomerular disease; glucocorticoids; gut-associated lymphoid tissue.
Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Source: PubMed