Efficacy and safety of sibeprenlimab in IgA nephropathy: interim analysis of the China cohort in the phase 3 VISIONARY trial.

BACKGROUND

Immunoglobulin A (IgA) nephropathy is a progressive immune-mediated chronic kidney disease with a high prevalence and disease burden in East Asia, including China. In a prespecified interim analysis (IA) of the global phase 3 VISIONARY trial, treatment with sibeprenlimab led to significant placebo-adjusted reduction in 24-hour urine protein-to-creatinine ratio (uPCR-24h) of 51.2% (P < .0001) at 9 months. Here, we report the interim efficacy and safety findings for sibeprenlimab for patients with IgA nephropathy enrolled from mainland China as part of the main global population.

METHODS

Patients (N = 102) were randomized 1:1 to receive sibeprenlimab 400 mg or placebo subcutaneously Q4W for 26 doses. Patients who completed the 9-month uPCR-24h assessment were included. The primary endpoint was change in uPCR-24h from baseline at 9 months. The key secondary endpoint of annualized estimated glomerular filtration rate slope over 24 months will be reported at trial completion. Other secondary and exploratory endpoints included spot urine protein-to-creatinine ratio (spot uPCR), proteinuria remission, haematuria resolution, reduction in biomarker levels [including galactose-deficient IgA1 (Gd-IgA1) and a proliferation-inducing ligand (APRIL)], and safety.

RESULTS

By the China IA data cutoff (January 2025), 42 patients from mainland China completed the 9-month uPCR-24h assessment (sibeprenlimab, n = 25; placebo, n = 17) and were included in the efficacy analysis. At 9 months, a reduction from baseline in uPCR-24h of 63.1% was observed in sibeprenlimab-treated patients versus a decrease of 3.1% in the placebo group, corresponding to a placebo-adjusted reduction of 61.9% (95% confidence interval 43.2%-74.5%). Spot uPCR declined by week 4 and was sustained through month 12. Sibeprenlimab reduced Gd-IgA1 (67.3%) and suppressed APRIL levels (97.7%) from baseline at week 48. The incidence of treatment-emergent adverse events was similar between treatment groups.

CONCLUSIONS

Interim efficacy and safety results for the mainland China cohort were consistent with the IA of the global cohort of the VISIONARY trial (ClinicalTrials.gov: NCT05248646).