Telitacicept Interim Phase 3 Trial in IgA Nephropathy

Key Takeaways

• Telitacicept was associated with a larger reduction in proteinuria than placebo at the interim 39-week assessment.
• Estimated glomerular filtration rate declined less with telitacicept than with placebo over the reported follow-up.
• Adverse events were more frequent overall, serious adverse events were less frequent, and no unexpected safety findings were reported.

In a prespecified interim analysis of a phase 3 trial, adults with biopsy-proven IgA nephropathy and persistent proteinuria despite supportive care had a 58.9% reduction in 24-hour urinary protein-to-creatinine ratio with telitacicept, compared with matching placebo in a randomized, double-blind setting.

This multicenter, double-blind, randomized, placebo-controlled study enrolled adults with biopsy-proven IgA nephropathy and persistent proteinuria of at least 1.0 g per day despite appropriate supportive care. A total of 318 patients were assigned in a 1:1 ratio, with 159 in each group. Participants received subcutaneous once-weekly telitacicept 240 mg or matching placebo. Telitacicept is a fusion protein that targets BAFF and APRIL.

At week 39, the percentage change in the 24-hour urinary protein-to-creatinine ratio was −58.9% with telitacicept and −8.8% with placebo. The relative difference, based on the ratio of geometric mean reductions between the two groups, was −55.0%, with a 95% confidence interval from −61.3 to −47.6 and a P value below 0.001. Estimated glomerular filtration rate changed by −1.0% with telitacicept and −7.7% with placebo relative to baseline. The 95% confidence intervals were −3.2 to 1.2 for telitacicept and −9.9 to −5.4 for placebo.

Adverse events occurred in 89.3% of patients receiving telitacicept and 78.6% of those receiving placebo. Serious adverse events were reported in 2.5% of the telitacicept group and 8.2% of the placebo group. No unexpected safety findings were reported with telitacicept.