- Title
- A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy
- Creator
- Mathur, Mohit; Barratt, Jonathon; Xia, Jing; Pereira, Brian J. G.; ENVISION Trial Investigators Group,; Chacko, Bobby; Chan, Tak Mao; Kooienga, Laura; Oh, Kook-Hwan; Sahay, Manisha; Suzuki, Yusuke; Wong, Muh Geot; Yarbrough, Jill
- Relation
- The New England Journal of Medicine Vol. 390, Issue 1, p. 20-31
- Publisher Link
- http://dx.doi.org/10.1056/NEJMoa2305635
- Publisher
- Massachusetts Medical Society
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- nephropathy; sibeprenlimab; monoclonal antibody; pathogenesis
- Identifier
- http://hdl.handle.net/1959.13/1495466
- Identifier
- uon:54017
- Identifier
- ISSN:0028-4793
- Language
- eng
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