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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Proteinuria; Proteinuric Kidney Disease; Proteinuria in Nephrotic Range; Proteinuric Renal Disease
• Intervention / Treatment: Drug: sparsentan; Drug: No sparsentan

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shruti Gupta, MD, MPH; Phone Number: 5712366626; Email: sgupta21@bwh.harvard.edu
• Study Contact Backup: Name: Api Chewcharat, MD, MPH; Phone Number: 857-930-5167; Email: achewcharat@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
      • Contact: Sophia L Wells; Phone Number: 330-802-5405; Email: swells8@bwh.harvard.edu
      • Principal Investigator: Api Chewcharat, MD, MPH
      • Contact: Shruti Gupta; Phone Number: 5712366626; Email: sgupta21@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment with sparsentan, an endothelin-1 antagonist; Participants will receive sparsentan 200 mg daily for 2 weeks, and will then titrate up to a target of 400 mg daily. After the Week 8 visit, patients will return to standard-of-care. We will compare the mean percent change in urine protein to creatinine ratio in patients treated with sparsentan versus historical controls who did not receive sparsentan.	Drug: sparsentan; 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.
Placebo Comparator: Historical controls with high-grade proteinuria not treated with sparsentan; Participants must meet all eligibility criteria, but did not receive sparsentan. Historical controls will be matched based on age, sex, race, stage and cancer type	Drug: No sparsentan; Historical controls who did not receive sparsentan, and are matched to patients who are treated with sparsentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urine to protein creatinine ratio (UPCR)	The geometric mean percent change in UPCR from screening day to Week 8	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VSPI discontinuation or interruption	Incidence of VSPI discontinuation or interruption in the 8 weeks following onset of high-grade proteinuria	8 weeks
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	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related adverse events including any of the following events	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; 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; 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; 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	8 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Travere Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 28, 2025
• First Submitted That Met QC Criteria: November 3, 2025
• First Posted (Actual): November 5, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: proteinuria; cancer; vascular endothelial growth factor inhibitors; endothelin-1 antagonist
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neoplasms; Proteinuria; sparsentan
• Other Study ID Numbers: 25-683

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a small, pilot study with patients with cancer receiving a specific cancer treatment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No