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Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy
Published on: October 13, 2023
A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy
Mohit Mathur1, Jonathan Barratt1, Bobby Chacko1
1From 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.).
Background:
A 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.
Methods:
In 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.
Results:
Among 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.
Conclusions:
In 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.).
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