IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study

Jonathan Barratt¹, Brad Rovin², Muh Geot Wong^{3

4}, Charles E Alpers⁵, Stewart Bieler⁶, Ping He⁶, Jula Inrig⁶, Radko Komers⁶, Hiddo J L Heerspink^{7

8}, Alex Mercer⁹, Irene L Noronha¹⁰, Jai Radhakrishnan¹¹, Michelle N Rheault¹², William Rote⁶, Howard Trachtman¹³, Hernán Trimarchi^{8

14}, Vlado Perkovic^{8

15}; PROTECT investigators

Affiliations

¹ Department of Cardiovascular Sciences, University of Leicester General Hospital, Leicester, UK.
² Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
³ Department of Renal Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia.
⁴ Concord Clinical School, University of Sydney, Concord, New South Wales, Australia.
⁵ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
⁶ Travere Therapeutics Inc., San Diego, California, USA.
⁷ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁸ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁹ JAMCO Pharma Consulting, Stockholm, Sweden.
¹⁰ Laboratory of Cellular, Genetic, and Molecular Nephrology, Division of Nephrology, University of São Paulo School of Medicine, São Paulo, Brazil.
¹¹ Division of Nephrology, Columbia University, New York, New York, USA.
¹² Division of Pediatric Nephrology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
¹³ Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
¹⁴ Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.
¹⁵ Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, New South Wales, Australia.

PMID: 37180506
PMCID: PMC10166729
DOI: 10.1016/j.ekir.2023.02.1086

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study

Jonathan Barratt et al. Kidney Int Rep. 2023.

. 2023 Mar 4;8(5):1043-1056.

doi: 10.1016/j.ekir.2023.02.1086. eCollection 2023 May.

Authors

Affiliations

¹ Department of Cardiovascular Sciences, University of Leicester General Hospital, Leicester, UK.
² Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
³ Department of Renal Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia.
⁴ Concord Clinical School, University of Sydney, Concord, New South Wales, Australia.
⁵ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
⁶ Travere Therapeutics Inc., San Diego, California, USA.
⁷ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁸ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁹ JAMCO Pharma Consulting, Stockholm, Sweden.
¹⁰ Laboratory of Cellular, Genetic, and Molecular Nephrology, Division of Nephrology, University of São Paulo School of Medicine, São Paulo, Brazil.
¹¹ Division of Nephrology, Columbia University, New York, New York, USA.
¹² Division of Pediatric Nephrology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
¹³ Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
¹⁴ Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.
¹⁵ Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, New South Wales, Australia.

PMID: 37180506
PMCID: PMC10166729
DOI: 10.1016/j.ekir.2023.02.1086

Abstract

Introduction: Sparsentan is a novel single-molecule dual endothelin angiotensin receptor antagonist with hemodynamic and anti-inflammatory properties and is not an immunosuppressant. The ongoing phase 3 PROTECT trial examines sparsentan in adults with IgA nephropathy (IgAN).

Methods: The PROTECT trial (NCT03762850) is a multicenter, international, randomized, double-blind, parallel-group, active-controlled study. The efficacy and safety of sparsentan versus the active control irbesartan is being evaluated in adults with biopsy-proven IgAN and proteinuria ≥1.0 g/d despite maximized treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) for at least 12 weeks. Blinded and aggregated baseline characteristics are reported descriptively and compared to contemporary phase 3 trials with patients with IgAN.

Results: The primary analysis population includes 404 patients who were randomized and received study drug (median age, 46 years). Enrolled patients were from Europe (53%), Asia Pacific (27%), and North America (20%). Baseline median urinary protein excretion was 1.8 g/d. The range of estimated glomerular filtration rate (eGFR) was broad with the largest proportion of patients (35%) in chronic kidney disease (CKD) stage 3B. Before transitioning to study medication, mean systolic/diastolic blood pressure was 129/82 mm Hg, with the majority of patients (63.4%) receiving the maximum labeled ACEi or ARB dose. Patients in Asian versus non-Asian regions included a higher percentage of females, had lower blood pressures, and included lower proportions of patients with a history of hypertension and baseline antihypertensive treatment.

Conclusions: Patient enrollment in PROTECT, with differing racial backgrounds and across CKD stages, will allow for important characterization of the treatment effect of sparsentan in patients with IgAN with proteinuria at high risk of kidney failure.

Keywords: dual endothelin angiotensin receptor antagonist; ethnicity; immunoglobulin A nephropathy; race; randomized controlled clinical trial; sparsentan.

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Figures

**Figure 1**
Patients receiving ACEi and ARB at screening at <50%, 50% to 80%, and >80% of MLD for patients on ACEi only, patients on ARB only, and patients on ACEi and ARB. For patients with more than 1 record of MLD percentage and for patients taking both ACEi and ARB treatment, the highest percentage MLD was included. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; MLD, maximum labeled dose.

See this image and copyright information in PMC

References

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IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study

Affiliations

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study

Authors

Affiliations

Abstract

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials