The New England journal of medicine · 2026
Ravulizumab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial.
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Barratt Jonathan, Farag Youssef M K, Rice Kara, Cammett Tobin J, Inker Lesley A, Trimarchi Hernán, Bruchfeld Annette, Heerspink Hiddo J L, Liew Adrian, Carroll Kevin, Zhang Hong, Norouzi Sayna, Hou Shuang, Park Sehoon, Pérez Valdivia Miguel Ángel, Radhakrishnan Jai, Suzuki Yusuke, Schneider Bonnie, Marsala John, Carrillo-Infante Cynthia, Lake Stephen L, Singh Ajay K, Nolan Stephen, Lafayette Richard A, I CAN Trial Group
Аннотация
BACKGROUND: In patients with IgA nephropathy, complement activation drives glomerular inflammation, which leads to hematuria, proteinuria, and nephron loss. Ravulizumab is a terminal complement inhibitor that prevents formation of C5a and C5b-9.
METHODS: In this phase 3 trial, we enrolled adults with IgA nephropathy who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area and proteinuria (24-hour urinary protein-to-creatinine ratio [with protein and creatinine both measured in grams] of ≥0.75 or total urinary protein excretion of ≥1.0 g per day), despite standard therapy. Patients were randomly assigned in a 1:1 ratio to receive an intravenous infusion of either ravulizumab or placebo every 8 weeks. In the prespecified interim analysis, the primary efficacy end point was the change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 34. Safety was also assessed.
RESULTS: In all, 485 patients underwent randomization, with 240 patients assigned to the ravulizumab group and 245 to the placebo group; 352 patients (176 in each group) were included in the interim analysis. In the ravulizumab group, the geometric mean 24-hour urinary protein-to-creatinine ratio at baseline and at week 34 was 1.56 and 0.83, respectively; in the placebo group, it was 1.60 and 1.48, respectively. At week 34, a significant reduction in the geometric mean 24-hour urinary protein-to-creatinine ratio was observed with ravulizumab (-46.6%) as compared with the reduction observed with placebo (-5.6%), corresponding to an adjusted geometric mean 24-hour urinary protein-to-creatinine ratio that was 43.4% (99% confidence interval, 30.1 to 54.2) lower with ravulizumab than with placebo (P<0.001). Adverse events occurred in 69.5% of the patients receiving ravulizumab and in 75.8% of those receiving placebo; serious adverse events occurred in 4.6% and 9.0%, respectively. No meningococcal infections or deaths occurred.
CONCLUSIONS: In adults with IgA nephropathy, ravulizumab resulted in a significantly greater reduction in the protein-to-creatinine ratio than placebo at week 34. (Funded by Alexion, AstraZeneca Rare Disease Unit; I CAN ClinicalTrials.gov number, NCT06291376; EU Clinical Trials number, 2023-507851-31-00.).
METHODS: In this phase 3 trial, we enrolled adults with IgA nephropathy who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area and proteinuria (24-hour urinary protein-to-creatinine ratio [with protein and creatinine both measured in grams] of ≥0.75 or total urinary protein excretion of ≥1.0 g per day), despite standard therapy. Patients were randomly assigned in a 1:1 ratio to receive an intravenous infusion of either ravulizumab or placebo every 8 weeks. In the prespecified interim analysis, the primary efficacy end point was the change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 34. Safety was also assessed.
RESULTS: In all, 485 patients underwent randomization, with 240 patients assigned to the ravulizumab group and 245 to the placebo group; 352 patients (176 in each group) were included in the interim analysis. In the ravulizumab group, the geometric mean 24-hour urinary protein-to-creatinine ratio at baseline and at week 34 was 1.56 and 0.83, respectively; in the placebo group, it was 1.60 and 1.48, respectively. At week 34, a significant reduction in the geometric mean 24-hour urinary protein-to-creatinine ratio was observed with ravulizumab (-46.6%) as compared with the reduction observed with placebo (-5.6%), corresponding to an adjusted geometric mean 24-hour urinary protein-to-creatinine ratio that was 43.4% (99% confidence interval, 30.1 to 54.2) lower with ravulizumab than with placebo (P<0.001). Adverse events occurred in 69.5% of the patients receiving ravulizumab and in 75.8% of those receiving placebo; serious adverse events occurred in 4.6% and 9.0%, respectively. No meningococcal infections or deaths occurred.
CONCLUSIONS: In adults with IgA nephropathy, ravulizumab resulted in a significantly greater reduction in the protein-to-creatinine ratio than placebo at week 34. (Funded by Alexion, AstraZeneca Rare Disease Unit; I CAN ClinicalTrials.gov number, NCT06291376; EU Clinical Trials number, 2023-507851-31-00.).