Sparsentan for Proteinuria

Overseen By Api Chewcharat, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brigham and Women's Hospital

Must be taking: VSPIs

Must not be taking: Endothelin inhibitors, Potassium-sparing diuretics

Disqualifiers: Kidney injury, Heart failure, Transplant, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether sparsentan can safely reduce high levels of protein in urine for cancer patients undergoing specific treatments. High protein levels in urine, known as proteinuria, pose a significant issue, and the study aims to determine if sparsentan can help. Participants will take sparsentan for several weeks, and their results will be compared to those of past patients who did not receive the drug. Ideal participants are cancer patients experiencing new high-grade proteinuria due to their cancer treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially beneficial treatment.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications to join the trial. The trial excludes participants who cannot stop taking specific medications like RAAS inhibitors, endothelin system inhibitors, potassium-sparing diuretics, antiarrhythmic medications, weight loss medications, St. John's wort, and strong CYP3A inhibitors.

Is there any evidence suggesting that sparsentan is likely to be safe for humans?

Research has shown that sparsentan is safe for humans. The FDA has approved it for treating proteinuria, a condition characterized by excessive protein in the urine, in patients with IgA nephropathy, a type of kidney disease. This approval indicates that sparsentan is generally well-tolerated.

In studies involving patients with conditions similar to those in the trial, sparsentan effectively reduced proteinuria. More patients experienced partial or complete remission of proteinuria with sparsentan compared to other treatments. These studies did not find any unexpected side effects, indicating its safety.

While specific data on side effects for this trial phase is not available, the existing approval and past studies suggest sparsentan is safe for people. However, like any treatment, some individuals might experience side effects. Participants should discuss potential risks with their healthcare providers before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sparsentan is unique because it targets proteinuria by acting as an endothelin-1 antagonist. Most treatments for proteinuria, such as ACE inhibitors or ARBs, primarily focus on managing blood pressure and reducing protein leakage indirectly. Sparsentan, on the other hand, directly inhibits endothelin-1, which plays a significant role in kidney function and protein leakage. This novel mechanism could potentially provide more direct and effective control over proteinuria, offering hope for better outcomes in patients who might not respond adequately to current therapies.

What evidence suggests that sparsentan might be an effective treatment for proteinuria?

Research has shown that sparsentan can help reduce proteinuria, which means having too much protein in urine. In studies, sparsentan significantly lowered urine protein levels in patients with conditions like IgA nephropathy and focal segmental glomerulosclerosis. For instance, one study found that 42% of patients experienced partial improvement in proteinuria with sparsentan, compared to 26% with irbesartan. Another study demonstrated that sparsentan helped three times more patients achieve complete improvement in proteinuria. In this trial, participants will receive sparsentan, and its effects on proteinuria will be compared to historical controls who did not receive sparsentan. These results suggest that sparsentan could be promising for reducing high protein levels in urine for patients undergoing certain cancer treatments. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

Adults with cancer and new high-grade proteinuria from taking VSPIs can join. They must be able to consent, not have a history of severe reactions to ARBs or ERAs, no recent heart or stroke issues, and their kidneys should work at a certain level. Pregnant women and those on conflicting meds or studies can't participate.

Inclusion Criteria

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 informed consent

I am 18 or older and being treated for cancer with VSPIs.

Exclusion Criteria

I cannot take certain blood pressure medicines during the trial's initial phase.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sparsentan, starting at 200 mg daily for 2 weeks, then titrating up to 400 mg daily, for a total of 8 weeks

8 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sparsentan

Trial Overview The study is testing if sparsentan can reduce severe protein leakage in the urine caused by cancer drugs that block VEGF signals. It's an open-label pilot study where all participants know they're getting sparsentan to see how effective and safe it is.

How Is the Trial Designed?

Group I: Treatment with sparsentan, an endothelin-1 antagonist Active Control 1 Intervention

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.

Group II: Historical controls with high-grade proteinuria not treated with sparsentan Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Travere Therapeutics, Inc.

Industry Sponsor

Trials

23

Recruited

103,000+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK616790

Sparsentan for treating primary IgA nephropathy - NCBI - NIH The primary outcome was the percentage change in UPCR from baseline to week 36. Sparsentan statistically significantly reduced proteinuria ...

2. medicalaffairs.travere.com medicalaffairs.travere.com/posters/duplex-proteinuria-remission-fsgs/

Sparsentan Improves Proteinuria in Focal Segmental ... Patients achieved partial remission of proteinuria earlier and more often with sparsentan vs maximum labeled dose irbesartan · Patients achieved ...

3. theisn.org theisn.org/blog/2024/03/18/protecting-iga-nephropathy-patients-sparsentan-reduces-proteinuria-and-preserves-kidney-function-through-to-two-years/

Protecting IgA Nephropathy Patients: Sparsentan Reduces ... The study met its primary efficacy endpoint, with sparsentan-treated participants having a significantly greater reduction in proteinuria from ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308550

Sparsentan versus Irbesartan in Focal Segmental ... At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan ...

5. filsparihcp.com filsparihcp.com/igan/efficacy/

Efficacy | FILSPARI® (sparsentan) The only 2-year, Phase 3 IgAN trial proven to deliver 3x more patients to complete remission of proteinuria (<0.3 g/day)3,5†.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843636/

Real-world assessment of sparsentan's drug safety framework Sparsentan has been approved for reducing proteinuria in adult patients with primary IgA nephropathy (IgAN) at risk of rapid disease progression ...