Sparsentan for high-grade proteinuria linked to VEGF inhibitors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a single-center, open-label pilot study in adults with active cancer who develop high-grade proteinuria while on VEGF pathway inhibitors. It uses a two-stage design to evaluate the efficacy and safety of sparsentan versus no sparsentan. Participants are adults with eGFR ≥ 45 ml/min/1.73 m2 and no prior ARB/ERA hypersensitivity, and they must have new or persistent proteinuria defined by dipstick or urine protein-to-creatinine ratio. The study compares sparsentan treatment to withholding sparsentan, with outcomes focusing on changes in proteinuria and renal safety. Brigham and Women's Hospital leads the trial with collaboration from Travere Therapeutics, aiming to inform whether sparsentan can mitigate kidney toxicity from cancer therapies that inhibit VEGF signaling.

Why it matters

Who can join: the full rules

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

Where it's running

• Brigham and Women's Hospital
  Boston, Massachusetts, United States Recruiting

Study contacts

• Study coordinator: Shruti Gupta, MD, MPH
• Email: sgupta21@bwh.harvard.edu
• Phone: 5712366626

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.