Sparsentan for the Treatment of VEGF Signaling Pathway Inhibitor-Associated Proteinuria

Inclusion criteria

• Adults (≥ 18 years old) with active malignancy who are currently treated with VSPIs
• New high-grade proteinuria, defined as ≥ 2+ proteinuria on dipstick or a calculated urinary protein-to-creatinine ratio ≥ 1.0 g/g
• Able to provide written inform consent

Exclusion criteria

• Estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73m2
• Baseline high grade proteinuria ≥ 2+ proteinuria on dipstick or a calculated urinary protein-to creatinine ratio or microalbumin-to-creatinine ≥ 1.0 g/g prior to VSPI initiation
• Acute kidney injury defined as serum creatinine at least 1.5 times above the most proximal serum creatinine prior to VSPIs initiation
• History of allergic reactions or angioedema to any angiotensin receptor blocker (ARB) or ERA, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications.
• Any potassium value >5 mEq/L in the 14 days preceding high-grade proteinuria
• History of organ transplantation, with the exception of corneal transplants.
• History of congestive heart failure (New York Heart Association Class II-IV)
• History of clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularization procedure) within 6 months prior to screening.
• Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or alanine aminotransferase and/or aspartate aminotransferase >2 times the upper limit of the normal at screening.
• Body weight <50 kg at screening
• Unable to hold renin-angiotensin-aldosterone system (RAAS) inhibitors such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), spironolactone, eplerenone, aliskiren, aldosterone blockers during run-in period
• Concomitant use of the following medications:

• Inhibitors of endothelin system such as ambrisentan, bosentan, macitentan
• Potassium-sparing diuretics such as amiloride, triamterene
• Antiarrhythmic medications such as amiodarone, digoxin
• Weight loss medications such as orlistat or amphetamine derivative agents
• St. John's wort or other hypericum-derived products
• Strong CYP3A inhibitors such as ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, ritonavir- or cobicistat-boosted regimens, boceprevir, telaprevir, conivaptan, mibefradil
• Pregnant or breastfeeding
• Concurrent participation in a study with an alternative experimental therapy that may interact with sparsentan
• Any condition that, in the view of the principal investigator, might place the patient at increased risk or compromise the integrity of the study
• Conflict with other study