Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial.
In the 2-year final analysis of the phase 3 PROTECT trial, sparsentan produced a sustained 40% greater reduction in proteinuria and slowed eGFR decline versus maximally titrated irbesartan in adults with IgA nephropathy, with a comparable safety profile.
Background
Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist. In the interim analysis of PROTECT it had significantly reduced proteinuria versus irbesartan at 36 weeks, and this report presents kidney function and outcomes over 110 weeks from the double-blind final analysis.
Study design
PROTECT was a double-blind, randomised, active-controlled, phase 3 study at 134 sites in 18 countries. Adults with biopsy-proven primary IgA nephropathy and proteinuria of at least 1.0 g/day despite maximised renin-angiotensin system inhibition were randomly assigned 1:1 to sparsentan (target 400 mg once daily) or irbesartan (target 300 mg once daily), with 203 patients in each group. Secondary endpoints included eGFR slope, proteinuria change, and a composite kidney failure outcome through 110 weeks.
Key findings
Patients on sparsentan had a slower eGFR decline: the chronic 2-year slope (weeks 6 to 110) was -2.7 versus -3.8 mL/min/1.73 m2 per year (difference 1.1, 95% CI 0.1 to 2.1; p=0.037), while the total slope difference of 1.0 did not reach significance (p=0.058). At 110 weeks, proteinuria was 40% lower with sparsentan than irbesartan. The composite kidney failure endpoint occurred in 18 of 202 (9%) sparsentan patients versus 26 of 202 (13%) irbesartan patients (relative risk 0.7, 95% CI 0.4 to 1.2). Treatment-emergent adverse events were well balanced with no new safety signals.
Clinical implications
Over 110 weeks, sparsentan versus maximally titrated irbesartan resulted in significant reductions in proteinuria and preservation of kidney function in IgA nephropathy. The findings support sparsentan as a non-immunosuppressive renoprotective option that lowers proteinuria without weakening the immune system in patients already optimised on RAS inhibition.
Category
Research
Source
Lancet
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