PROTECT Subgroup Analysis: Sparsentan Provides Clinical Benefits vs Irbesartan in Patients With IgA Nephropathy With Proteinuria Above and Below 1 g/g

About the research

Summary

Aim

To determine the treatment effects of sparsentan versus the maximum labeled dose irbesartan in patients with IgA nephropathy between patients subgroups with baseline urine protein-creatinine ratio (UPCR) <1.0 and ≥1.0 g/g¹

Figure. PROTECT study design

PROTECT is a large, international, randomized, double-blind, active-controlled Phase 3 trial to assess the efficacy and safety of sparsentan versus irbesartan. This analysis evaluates subgroups of UPCR <1 versus ≥1 g/g at baseline<sup>1

a</sup>95% and 97% of patients titrated to maximum labeled dose of sparsentan and irbesartan, respectively.¹

About the figure

Participants were randomly assigned to the treatment, sparsentan or active-control, maximum labeled dose irbesartan group¹

Study included a 110-week double-blind treatment period and 4 weeks of no treatment. Interim analysis occurred at 36 weeks. Two-year follow-up occurred at 110 weeks. There was an inclusion criterion of urinary protein excretion (UPE) ≥1 g/day at screening¹

Key findings

Patient demographics and baseline characteristics were well balanced between treatment arms¹

Sparsentan demonstrated superior rapid and sustained reductions in UPCR regardless of baseline UPCR levels versus maximum labeled dose irbesartan¹


Similarly, complete remission (CR) of proteinuria was achieved earlier and more frequently in patients treated with sparsentan versus maximum labeled dose irbesartan regardless of baseline UPCR level¹

Figure. LS mean change from baseline in UPCR for the population with UPCR <1 g/g and UPCR ≥1 g/g

At Week 110, patients with a baseline UPCR <1.0 g/g showed a 34.4% reduction when treated with sparsentan versus a 13.9% increase with maximum labeled dose irbesartan¹

At Week 110, patients with a baseline UPCR ≥1.0 g/g showed a 48.2% reduction when treated with sparsentan versus a 12.5% reduction with maximum labeled dose irbesartan¹

About the figure

In patients with baseline UPCR <1.0 g/g, sparsentan led to a 42% relative reduction versus maximum labeled dose irbesartan with a ratio of 0.58 (95% CI: 0.43 to 0.77)¹

In patients with baseline UPCR ≥1.0 g/g, sparsentan led to a 41% relative reduction versus maximum labeled dose irbesartan with a ratio of 0.59 (95% CI: 0.47 to 0.75)¹

Greater kidney function preservation with sparsentan was consistently seen regardless of baseline UPCR level¹

Absolute change in estimated glomerular filtration rate (eGFR) from baseline to Week 110 was lower with sparsentan versus maximum labeled irbesartan¹

Figure. LS mean change from baseline in eGFR for the overall study, UPCR <1 g/g, and UPCR ≥1 g/g populations

In the overall population, sparsentan demonstrated a difference of 3.7 mL/min per 1.73 m². In the population with baseline UPCR <1.0 g/g, sparsentan demonstrated a difference of 1.9 mL/min per 1.73 m². In the population with baseline UPCR ≥1.0 g/g, sparsentan demonstrated a difference of 4.2 mL/min per 1.73 m²

About the figure

In the overall population, sparsentan demonstrated a -5.8 mL/min per 1.73 m² decrease in eGFR versus a -9.5 mL/min per 1.73 m² decrease with maximum labeled dose irbesartan (Difference: 3.7, 95% CI: 1.45 to 5.99)¹

In the population with baseline UPCR <1.0 g/g, sparsentan demonstrated a -4.1 decrease in eGFR versus a -6.0 mL/min per 1.73 m² decrease with maximum labeled dose irbesartan (Difference: 1.9, 95% CI: 1.96 to 5.69)¹

In the population with baseline UPCR ≥1.0 g/g, sparsentan demonstrated a -7.1 mL/min per 1.73 m² decrease in eGFR versus a -11.3 mL/min per 1.73 m² decrease with maximum labeled dose irbesartan (Difference: 4.2, 95% CI: 1.39 to 7.05)¹

Sparsentan was well tolerated with a consistent safety profile comparable to maximum labeled dose irbesartan across baseline proteinuria subgroups¹

The most common adverse events (AEs) [≥15% of patients in any group] were: 

Table. Treatment-emergent adverse events (TEAE) and treatment discontinuations due to an AE

In the population with baseline UPCR <1.0 g/g, 90% (69/77) of patients on sparsentan and 85% (58/68) of patients on maximum labeled dose irbesartan experienced a TEAE¹

In the population with baseline UPCR ≥1.0 g/g, 94% (118/125) of patients on sparsentan and 89% (119/134) of patients on maximum labeled dose irbesartan experienced a TEAE¹

About the figure

In the population with baseline UPCR <1.0 g/g, 8% (6/77) of patients on sparsentan and 3% (2/68) of patients on maximum labeled dose irbesartan discontinued treatment due to an AE¹

In the population with baseline UPCR ≥1.0 g/g, 10% (13/125) of patients on sparsentan and 12% (16/134) of patients on maximum labeled dose irbesartan discontinued treatment due to an AE¹

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Footnotes

PROTECT trial was conducted during the COVID-19 pandemic.

AE, adverse event; CI, confidence interval; COVID-19, coronavirus disease 2019; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; IgA, immunoglobulin A; IRB, irbesartan; KDIGO, Kidney Disease Improving Global Outcomes; LS, least square; SPAR, sparsentan; TEAE, treatment-emergent adverse event; UPCR, urine protein-creatinine ratio;
UPE, urinary protein excretion.

MA-SP-24-0133 | November 2024