Efficacy and Safety of Sparsentan Versus Irbesartan in Patients with IgA Nephropathy (PROTECT): 2-Year Results From a Randomised Active-Controlled Phase 3 Trial
The Lancet – 2023
Implementing the Kidney Health Initiative Surrogate Efficacy Endpoint in Patients with IgA Nephropathy (the PROTECT Trial)
Journal article
Published on August 19, 2019
Contributors:
Barratt J, Rovin BH, Diva U et al.
Barratt J, Rovin BH, Diva U et al.
DOI:
10.1016/j.ekir.2019.08.007
10.1016/j.ekir.2019.08.007
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 limited1
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 endpoints1-3
A scientific workshop, co-sponsored by the NKF, FDA, and EMA, evaluated change in albuminuria and rate of change (i.e. slope) in glomerular filtration rate (GFR) as surrogate endpoints.1,2 The KHI, comprised of the American Society of Nephrology and the FDA, identified proteinuria reduction as a surrogate endpoint.1,3
The sparsentan PROTECT trial is the first study to incorporate the NKF and KHI recommendations1
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).1,3 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 Weeks 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 trial incorporated a more time-efficient study design.1
The PROTECT trial also incorporated innovative strategies to promote patient recruitment and retention1
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, Inc. 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
Related Content
Efficacy and Safety of Sparsentan Versus Irbesartan in Patients with IgA Nephropathy (PROTECT): 2-Year Results From a Randomised Active-Controlled Phase 3 Trial
The Lancet – 2023
Sparsentan in Patients With IgA Nephropathy: A Prespecified Interim Analysis From a Randomised, Double-Blind, Active-Controlled Clinical Trial
The Lancet – 2023
Association Between Complete Proteinuria Remission and Kidney Function in Phase 3 PROTECT Trial of Sparsentan in IgA Nephropathy
Clinical Journal of the American Society of Nephrology – 2025
Footnotes
The PROTECT study was supported by Retrophin, Inc. (now Travere Therapeutics, Inc.). Please see the publication for the full list of disclosures.
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.
- Barratt J et al. Kidney Int Rep. 2019;4(11):1633-1637.
- Inker LA, Heerspink HL. Am J Kidney Dis. 2018;72:771-773.
- Thompson A et al. Clin J Am Soc Nephrol. 2019;14:469-481.
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