• Mohit Mathur, Jonathan Barratt, Bobby Chacko, Tak Mao Chan, Laura Kooienga, Kook-Hwan Oh, Manisha Sahay, Yusuke Suzuki, Muh Geot Wong, Jill Yarbrough, Jing Xia, PereiraBrian J GBJGFrom Visterra, Waltham, MA (M.M., J.Y., B.J.G.P.); John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom (J.B.); Nephrology and Transplantation, John Hunter Hospital and University of Newcastle, Newcastle, NSW (B., and ENVISION Trial Investigators Group.
• From Visterra, Waltham, MA (M.M., J.Y., B.J.G.P.); John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom (J.B.); Nephrology and Transplantation, John Hunter Hospital and University of Newcastle, Newcastle, NSW (B.C.), and the University of Sydney, Sydney (M.G.W.) - both in Australia; the University of Hong Kong, Queen Mary Hospital, Hong Kong (T.M.C.); Colorado Kidney Care, Denver (L.K.); Seoul National University College of Medicine, Seoul, South Korea (K.-H.O.); Osmania General Hospital, Hyderabad, India (M.S.); the Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo (Y.S.); and Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ (J.X.).
• N. Engl. J. Med. 2024 Jan 4; 390 (1): 203120-31.

BackgroundA proliferation-inducing ligand (APRIL) is implicated in the pathogenesis of IgA nephropathy. Sibeprenlimab is a humanized IgG2 monoclonal antibody that binds to and neutralizes APRIL.MethodsIn this phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned adults with biopsy-confirmed IgA nephropathy who were at high risk for disease progression, despite having received standard-care treatment, in a 1:1:1:1 ratio to receive intravenous sibeprenlimab at a dose of 2, 4, or 8 mg per kilogram of body weight or placebo once monthly for 12 months. The primary end point was the change from baseline in the log-transformed 24-hour urinary protein-to-creatinine ratio at month 12. Secondary end points included the change from baseline in the estimated glomerular filtration rate (eGFR) at month 12. Safety was also assessed.ResultsAmong 155 patients who underwent randomization, 38 received sibeprenlimab at a dose of 2 mg per kilogram, 41 received sibeprenlimab at a dose of 4 mg per kilogram, 38 received sibeprenlimab at a dose of 8 mg per kilogram, and 38 received placebo. At 12 months, the geometric mean ratio reduction (±SE) from baseline in the 24-hour urinary protein-to-creatinine ratio was 47.2±8.2%, 58.8±6.1%, 62.0±5.7%, and 20.0±12.6% in the sibeprenlimab 2-mg, 4-mg, and 8-mg groups and the placebo group, respectively. At 12 months, the least-squares mean (±SE) change from baseline in eGFR was -2.7±1.8, 0.2±1.7, -1.5±1.8, and -7.4±1.8 ml per minute per 1.73 m2 in the sibeprenlimab 2-mg, 4-mg, and 8-mg groups and the placebo group, respectively. The incidence of adverse events that occurred after the start of administration of sibeprenlimab or placebo was 78.6% in the pooled sibeprenlimab groups and 71.1% in the placebo group.ConclusionsIn patients with IgA nephropathy, 12 months of treatment with sibeprenlimab resulted in a significantly greater decrease in proteinuria than placebo. (Funded by Visterra; ENVISION ClinicalTrials.gov number, NCT04287985; EudraCT number, 2019-002531-29.).Copyright © 2023 Massachusetts Medical Society.

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