Study design for the APPLAUSE clinical trial for FABHALTA® (iptacopan)

TO SLOW KIDNEY FUNCTION DECLINE IN ADULTS WITH PRIMARY IgAN AT RISK OF DISEASE PROGRESSION¹

• Study design: A randomized, placebo-controlled, double-blind, multicenter, global study

• Study population: Adults with biopsy-proven primary IgAN (median time from biopsy: ~1 year)

  • eGFR ≥20 mL/min/1.73 m²

  • Elevated proteinuria (UPCR ≥1 g/g)

  • Patients were primarily treated with a stable dose of maximally tolerated RASi therapy with or without a stable dose of an SGLT2i

  • Patients were included in either the main study population (eGFR ≥30 mL/min/1.73 m²) or the severe renal impairment population (eGFR ≥20 and <30 mL/min/1.73 m²)

  • Rescue immunosuppressive treatment could be initiated per investigator discretion during the trial

^aNot all MEST-C components were available for all patients. No major imbalances in MEST-C score categories were noted between treatment groups. More participants in the iptacopan group had podocyte hypertrophy (16% vs 8.7%) and crescents (C1: 25.2% vs 19.7%) at the time of their qualifying biopsy compared to placebo.^2
bHematuria was based on urine dipstick test and not available for all patients.¹

SELECTED KEY INCLUSION CRITERIA^1,2:

• Patients ≥18 years of age with biopsy-proven IgAN

  • Biopsy anytime for eGFR 20 to <30 mL/min/1.73 m²

  • Biopsy within 5 years for eGFR ≥45 mL/min/1.73 m²

  • Biopsy within 2 years (with <50% tubulointerstitial fibrosis) for eGFR 30 to <45 mL/min/1.73 m²

• Proteinuria (UPCR ≥1 g/g) at screening and run-in period

• On a stable dose of maximally tolerated RASi therapy ± a stable dose of an SGLT2i

• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae. Recommendation to be vaccinated against Haemophilus influenzae type b

SELECTED KEY EXCLUSION CRITERIA^1-3:

• Any secondary IgAN

• Patients with other glomerulopathies

• Previous treatment with immunosuppressive agents or other immunomodulatory agents within 90 days before the first study drug administration

• SBP >140 mm Hg or DBP >90 mm Hg at randomization

• Bacterial, viral, or fungal infection within 14 days before randomization

• Prior transplantation (any organ, including bone marrow)

TO SLOW KIDNEY FUNCTION DECLINE IN ADULTS WITH PRIMARY IgAN AT RISK OF DISEASE PROGRESSION¹

*The run-in period allowed for dose adjustment of ACEi/ARB treatments to either the locally approved maximal daily dose or the maximally tolerated dose and administration of vaccinations. Study treatment began when a patient had received 90 days of ACEi/ARB treatment at these levels and at least 2 weeks had elapsed since completion of vaccinations.<sup>1,4

†</sup>Performed when the first 250 patients randomized from main study population reached Month 9 or discontinued the study.¹

KEY SECONDARY END POINT¹

• Time to first occurrence of a kidney composite event, defined as reaching either:

  • Sustained^‡ ≥30% decline in eGFR from baseline,

  • Sustained^‡ eGFR <15 mL/min/1.73 m²,

  • Maintenance^‡ dialysis,

  • Receipt of kidney transplant, or

  • Death from kidney failure

^‡Over at least 4 weeks.

EXPLORATORY END POINTS²

• Relative change from baseline in 24-hour UPCR at Month 9 and Month 24

• Geometric mean percent change from baseline in UPCR first morning void (FMV) by visit