APPLAUSE-IgAN
Trial question
What is the role of iptacopan in patients with IgA nephropathy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
48.0% female
52.0% male
N = 250
250 patients (119 female, 131 male).
Inclusion criteria: adult patients with biopsy-confirmed IgA nephropathy and proteinuria despite optimized supportive therapy.
Key exclusion criteria: secondary IgA nephropathy; SBP > 140 mmHg or DBP > 90 mmHg; previous treatment with immunosuppressive or other immunomodulatory agents; prior use of iptocopan; active systemic bacterial, viral, or fungal infection in the past 14 days.
Interventions
N=125 iptacopan (oral dose of 200 mg BID for 24 months plus supportive therapy).
N=125 placebo (matching placebo for 24 months plus supportive therapy).
Primary outcome
Geometric mean reduction in 24-hour urinary protein-to-creatinine ratio at 9 months
41.2%
9.2%
41.2 %
30.9 %
20.6 %
10.3 %
0.0 %
Iptacopan
Placebo
Significant
increase ▲
NNT = 3
Significant increase in geometric mean reduction in 24-hour urinary protein-to-creatinine ratio at 9 months (41.2% vs. 9.2%; MD 38.3, 95% CI 26 to 48.6).
Secondary outcomes
Significant increase in the proportion of patients with urinary protein-to-creatinine ratio < 1 at 9 months without receiving rescue or alternative medication or undergoing RRT (42.5% vs. 21.9%; OR 3.12, 95% CI 1.68 to 5.79).
Significant increase in the proportion of patients with urinary protein-to-creatinine ratio < 0.5 at 9 months without receiving rescue or alternative medication or undergoing RRT (14.2% vs. 6.2%; OR 2.66, 95% CI 1.04 to 6.78).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult patients with biopsy-confirmed IgA nephropathy and proteinuria despite optimized supportive therapy, iptacopan was superior to placebo with respect to geometric mean reduction in 24-hour urinary protein-to-creatinine ratio at 9 months.
Reference
Vlado Perkovic, Jonathan Barratt, Brad Rovin et al. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N Engl J Med. 2024 Oct 25. Online ahead of print.
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