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
IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study
Journal article
Published on March 4, 2023
Contributors:
Barratt J, Rovin B, Wong MG et al.
Barratt J, Rovin B, Wong MG et al.
DOI:
10.1016/j.ekir.2023.02.1086
10.1016/j.ekir.2023.02.1086
Summary
The large, interventional, Phase 3 sparsentan PROTECT trial will provide long-term data on sparsentan in IgA nephropathy across a geographically diverse global cohort1
Background
IgA nephropathy is the most common primary glomerulopathy worldwide.1-3 It is a heterogeneous disease that often progresses to kidney failure.1,4
Historically, treatment options have included renin angiotensin system inhibitors (RASi) and angiotensin receptor blockers (ARBs).1
RASi have a known nephroprotective effect, and models of kidney disease have demonstrated a therapeutic effect with endothelin type A receptor antagonists.1,5,6 Together these treatments can target two key pathways in IgA nephropathy.1,6
Sparsentan is a non-immunosuppressive, single-molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA).1,7,8
Aim
The objective of the Phase 3 PROTECT study is to evaluate the long-term efficacy and safety of sparsentan compared with the active comparator irbesartan in IgA nephropathy.1 This manuscript describes the baseline characteristics.1
Approach
PROTECT is a large, international, randomized, double-blind, active-controlled Phase 3 trial in IgA nephropathy of sparsentan 400 mg versus irbesartan 300 mg.1 Key eligibility criteria included1:
- Biopsy-proven primary IgA nephropathy
- Proteinuria ≥1 g/day
- Estimated glomerular filtration (eGFR) ≥30 ml/min per 1.73 m2
- Maximum tolerated (stable) dose of ACEi and/or ARB therapy for ≥12 weeks
Baseline characteristics were analyzed, compared between Asian and non-Asian geographic regions, and compared to other IgA nephropathy trials.1
Findings
Baseline characteristics
Randomized and treated patients (N=404) were primarily White (67.3%, 272/404), non-Hispanic (91.1%, 368/404) adult males (69.8%, 282/404) with a median age of 46 years.1
Patients were from Europe (53%), Asia Pacific (27%), and North America (20%).1
Key baseline clinical and laboratory assessments included1:
- Median time of initial kidney biopsy: 4.0 years before enrollment
- History of hypertension: 76.5% (309/404) of patients
- Mean systolic/diastolic blood pressure: 129/82.4 mmHg
- Median urine protein-to-creatinine ratio (UPCR): 1.2 g/g
- Median urine albumin-to-creatinine ratio (UACR): 1.1 g/g
eGFR varied with the largest portion of patients (35.1%, 142/404) having eGFR corresponding to stage 3b chronic kidney disease (CKD).1
Prior to receiving the study treatment, 63.4% (256/404) of patients were receiving the maximum labeled ACEi or ARB dose.1
Key takeaway
Patients enrolled in the sparsentan PROTECT trial were racially diverse and demonstrated varying stages of CKD.1 The sparsentan PROTECT trial identified the treatment effect of sparsentan across a heterogeneous, high-risk, IgA nephropathy population.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
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
Sparsentan in Patients With IgA Nephropathy: A Prespecified Interim Analysis From a Randomised, Double-Blind, Active-Controlled Clinical Trial
The Lancet – 2023
Footnotes
This study was funded by Travere Therapeutics, Inc. Please see the publication for the full list of disclosures.
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CKD, chronic kidney disease; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; FDA, Food and Drug Administration; IgA, immunoglobulin A; RAAS, renin angiotensin-aldosterone system; UACR, urine albumin-creatinine ratio; UPCR, urine protein-creatinine ratio.
- Barratt J et al. Kidney Int Rep. 2023;8(5):1043-1056.
- McGrogan A et al. Nephrol Dial Transplant. 2011;26:414-430.
- Schena FP, Nistor I. Semin Nephrol. 2018;38:435-442.
- Barbour SJ et al. Kidney Int. 2013;84:1017-1024.
- Kohan DE. Kidney Int. 2014;86:896-904.
- Komers R et al. Am J Physiol Regul Integr Comp Physiol. 2016;310(10):R877-R784.
- Kowala MC et al. J Pharmacol Exp Ther. 2004;309:275-284.
- Trachtman H et al. Drugs Future. 2020;45:79-98.
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