Single-center, open-label, two-stage pilot study examining the efficacy and safety of sparsentan for reducing high-grade proteinuria among patients with cancer who receive vascular endothelial growth factor inhibitors
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
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.
Single group
sparsentan
DrugParticipants will receive sparsentan 200 mg daily for 2 weeks, and will then titrate up to a target of 400 mg daily. Safety and feasibility will be assessed. The mean percent change in urine protein to creatinine ratio will be assessed from screening to week 8, and compared to historical controls not treated with sparsentan.
No sparsentan
DrugHistorical controls who did not receive sparsentan, and are matched to patients who are treated with sparsentan
Change in urine to protein creatinine ratio (UPCR)
The geometric mean percent change in UPCR from screening day to Week 8
VSPI discontinuation or interruption
Incidence of VSPI discontinuation or interruption in the 8 weeks following onset of high-grade proteinuria
Resolution of Proteinuria
Incidence of resolution of high-grade proteinuria, defined as recovery of UPCR \< 0.5 g/g in the 8 weeks following onset of high-grade proteinuria
Incidence of treatment-related adverse events including any of the following events
1. Hyperkalemia defined as serum potassium ≥ 5.5 mmol/L on two separate occasion after ruling out measurement errors and alternative causes and despite appropriate use of diuretics and dietary modification 2. Hypotension defined as decrease in systolic blood pressure ≥20 mm Hg or diastolic blood pressure by ≥10 mm Hg from pre-sparsentan baseline with new dizziness after excluding alternative causes unrelated to sparsentan or determined at the discretion of treating physician 3. AKI defined as serum creatinine persistently ≥ 1.5-fold from pre-sparsentan baseline on 2 consecutive lab checks after excluding alternative causes unrelated to sparsentan or determined at the discretion of treating physician 4. Elevated liver function test defined as newly developed AST or ALT ≥ 3 times of the ULN, with or without an elevation of total serum bilirubin ≥ 2 times ULN after sparsentan initiation
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Brigham and Women's Hospital
Lead sponsor
Travere Therapeutics, Inc.
Collaborator
