APPLAUSE-IgAN is a phase 3, randomized double-blind, placebo-controlled trial that included patients with biopsy-confirmed IgAN and proteinuria of at least 1 g/g (n=477), despite supportive care. Patients randomly received (1:1) iptacopan 200 mg or placebo twice a day for 24 months and continued to receive supportive treatment.
The exploratory end points of the trial included changes from baseline in complement biomarkers, such as urinary sC5b-9, serum Wieslab activity, C3, and C4. Researchers also evaluated the changes in galactose-deficient IgA1 (Gd-IgA1) and urinary sCD163 in the interim analysis population at month 9.
At month 24, researchers observed a reduction in Wieslab activity and urinary sC5b-9 and increased serum C3 after treatment with iptacopan. C4 levels were unchanged and were consistent with the findings from month 9. In addition, in the iptacopan arm, levels of Gd-IgA1 remained unchanged from baseline. The reduction in sCD163 from baseline was greater in the iptacopan arm than in the placebo arm.
“Sustained modulation of complement biomarkers at M9 [month 9] and M24 [month 24] indicates that iptacopan selectively and durably inhibits the AP. As expected from iptacopan’s proposed mechanism of action, Gd-IgA1 was not affected,” the researchers concluded. “The reduction in urinary sCD163 suggests that iptacopan also attenuates glomerular inflammation in patients with IgAN.”