Proteinuria, Proteinuria in Nephrotic Range, Proteinuric Kidney Disease, Proteinuric Renal Disease
Conditions
Keywords
vascular endothelial growth factor inhibitors, cancer, proteinuria, endothelin-1 antagonist
Brief summary
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
Interventions
DRUGsparsentan
Participants 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.
DRUGNo sparsentan
Historical controls who did not receive sparsentan, and are matched to patients who are treated with sparsentan
Sponsors
Brigham and Women's Hospital
Travere Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults (≥ 18 years old) with active malignancy who are currently treated with VSPIs 2. New high-grade proteinuria, defined as ≥ 2+ proteinuria on dipstick or a calculated urinary protein-to-creatinine ratio ≥ 1.0 g/g 3. Able to provide written inform consent
Exclusion criteria
1. Estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73m2 2. 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 3. Acute kidney injury defined as serum creatinine at least 1.5 times above the most proximal serum creatinine prior to VSPIs initiation 4. 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. 5. Any potassium value \>5 mEq/L in the 14 days preceding high-grade proteinuria 6. History of organ transplantation, with the exception of corneal transplants. 7. History of congestive heart failure (New York Heart Association Class II-IV) 8. 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. 9. 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. 10. Body weight \<50 kg at screening 11. 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 12. Concomitant use of the following medications: 1. Inhibitors of endothelin system such as ambrisentan, bosentan, macitentan 2. Potassium-sparing diuretics such as amiloride, triamterene 3. Antiarrhythmic medications such as amiodarone, digoxin 4. Weight loss medications such as orlistat or amphetamine derivative agents 5. St. John's wort or other hypericum-derived products 6. Strong CYP3A inhibitors such as ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, ritonavir- or cobicistat-boosted regimens, boceprevir, telaprevir, conivaptan, mibefradil 13. Pregnant or breastfeeding 14. Concurrent participation in a study with an alternative experimental therapy that may interact with sparsentan 15. Any condition that, in the view of the principal investigator, might place the patient at increased risk or compromise the integrity of the study 16. Conflict with other study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in urine to protein creatinine ratio (UPCR) | 8 weeks | The geometric mean percent change in UPCR from screening day to Week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VSPI discontinuation or interruption | 8 weeks | Incidence of VSPI discontinuation or interruption in the 8 weeks following onset of high-grade proteinuria |
| Resolution of Proteinuria | 8 weeks | 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 |
Countries
United States
Contacts
CONTACTShruti Gupta, MD, MPH
CONTACTApi Chewcharat, MD, MPH
Outcome results
None listed