Summary

The sparsentan PROTECT trial incorporated surrogate endpoint recommendations from the National Kidney Foundation (NKF) and the Kidney Health Initiative (KHI)¹

The development and regulatory approval of novel therapies for glomerular diseases has been limited.¹

The nature of glomerular diseases, challenges with clinical trial design, and traditional endpoint requirements by regulatory authorities have been barriers in bringing novel therapies to clinical practice.¹

The National Kidney Foundation (NKF), US Food and Drug Administration (FDA), European Medicines Agency (EMA), and the Kidney Health Initiative (KHI) identified surrogate endpoints to replace traditionally required clinical endpoints.^2,3

A scientific workshop, co-sponsored by NKF, FDA, and EMA, evaluated change in albuminuria and rate of change (i.e. slope) in glomerular filtration rate (GFR) as surrogate endpoints.² The KHI, comprised of the American Society of Nephrology and the FDA, identified proteinuria reduction as a surrogate endpoint.³

The sparsentan PROTECT trial is the first study to incorporate the NKF and KHI recommendations.¹

The PROTECT trial incorporated reduction in proteinuria at Week 36 as the primary endpoint.¹ Proteinuria can reflect the therapeutic effect on progression to end-stage kidney disease (ESKD).³ The PROTECT trial was powered to detect a 30% difference in proteinuria between sparsentan and the active comparator, irbesartan.¹

Rate of change in estimated glomerular filtration (eGFR) at Week 110 and Week 114 was incorporated as a confirmatory endpoint as it is statistically more efficient and allows for shorter, smaller, and more feasible clinical trials.¹ The PROTECT study design represents a more time-efficient study design.¹

The PROTECT trial also incorporated innovative strategies to promote patient recruitment and retention.¹

Findings from a patient focus group were assessed and integrated into the PROTECT study design.¹ Patients frequently requested limiting the number of hospital visits, especially during a 24-hour urine collection.¹ Travere Therapeutics implemented a delivery and collection service from the patient’s home or place of work.¹

Additionally, real-time collaboration was encouraged amongst study sites and coordinators.¹

Key takeaway

The sparsentan PROTECT trial is the first study to incorporate the NKF and KHI recommendations.¹ The PROTECT study design also represents a more time-efficient and patient-friendly model for studying novel therapies, like sparsentan, in glomerular diseases.¹

Footnotes

eGFR, estimated glomerular filtration rate; EMA, European Medicines Agency; ESKD, end-stage kidney disease; FDA, Food and Drug Administration; IgA, immunoglobulin A; KHI, Kidney Health Initiative; NKF, National Kidney Foundation; UPCR, urine protein-creatinine ratio.

MA-SP-24-0054 | August 2024