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

NCT07224776 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 25-683
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Proteinuria in Nephrotic Range; Proteinuric Kidney Disease; Proteinuria; Proteinuric Renal Disease

Keywords

vascular endothelial growth factor inhibitors; cancer; proteinuria; endothelin-1 antagonist

Outcome Measures

Primary Outcomes (1)

• Change in urine to protein creatinine ratio (UPCR)

  The geometric mean percent change in UPCR from screening day to Week 8

  8 weeks

Secondary Outcomes (2)

• VSPI discontinuation or interruption

  8 weeks

• Resolution of Proteinuria

  8 weeks

Other Outcomes (1)

• Incidence of treatment-related adverse events including any of the following events

  8 weeks

Study Arms (2)

Treatment with sparsentan, an endothelin-1 antagonist

ACTIVE COMPARATOR

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

Historical controls with high-grade proteinuria not treated with sparsentan

PLACEBO COMPARATOR

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

Interventions

sparsentan DRUG

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.

Treatment with sparsentan, an endothelin-1 antagonist

No sparsentan DRUG

Historical controls who did not receive sparsentan, and are matched to patients who are treated with sparsentan

Historical controls with high-grade proteinuria not treated with sparsentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Travere Therapeutics, Inc.: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Proteinuria; Neoplasms

Interventions

sparsentan

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Shruti Gupta, MD, MPH

CONTACT

5712366626; sgupta21@bwh.harvard.edu

Api Chewcharat, MD, MPH

CONTACT

857-930-5167; achewcharat@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Onconephrology

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: November 5, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)