Sparsentan for Proteinuric Kidney Disease

(EPPIK Trial)

Recruiting at 45 trial locations

Overseen By Travere Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Travere Therapeutics, Inc.

Must be taking: ACEI, ARB

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Heart failure, Liver disease, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 108 weeks

67 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called sparsentan to assess its safety and effectiveness for treating certain kidney diseases that cause high protein levels in urine. The study divides participants into groups based on different kidney conditions: one group includes those with specific glomerular diseases, while others focus on conditions like IgA nephropathy or genetic kidney disorders. Suitable candidates have a confirmed kidney diagnosis and high protein levels in their urine despite current treatments. Participants will take sparsentan daily for about two years to determine if it reduces protein levels and improves kidney health. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in kidney disease treatment.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you need any prohibited medications or if you are on chronic immunosuppressive medications that haven't been stable for at least a month before screening.

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

Research has shown that sparsentan is generally safe for people. In a study involving patients with focal segmental glomerulosclerosis (FSGS), sparsentan reduced protein in the urine without major safety issues. The FDA granted fast-track approval for patients with immunoglobulin A nephropathy (IgAN) who are at risk of rapid disease progression, suggesting its safety for use.

While researchers continue to study sparsentan, previous research has not reported any major side effects, indicating it is relatively safe based on current information. However, ongoing research will offer more details about its long-term safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Sparsentan is unique because it combines two mechanisms of action in one molecule: it blocks both the endothelin and angiotensin receptors. These pathways are crucial in kidney diseases like IgAN, IgAV, AS, FSGS, and MCD, which often lead to excess protein in the urine. Unlike standard treatments that usually address just one pathway, sparsentan's dual-action approach holds the promise of more effectively reducing proteinuria and potentially protecting kidney function over time. Researchers are excited because this could mean better outcomes for patients who have limited options right now.

What evidence suggests that sparsentan might be an effective treatment for proteinuric kidney disease?

Research has shown that sparsentan effectively lowers protein levels in urine for various kidney conditions. In this trial, participants will be divided into groups based on their specific kidney condition. For IgA nephropathy, studies indicate that sparsentan reduces urine protein by 62% after 14 weeks. In cases of focal segmental glomerulosclerosis (FSGS), sparsentan significantly reduces urine protein in just eight weeks. Sparsentan blocks certain harmful pathways in the kidney, helping to protect kidney function. This treatment shows promise in managing these kidney diseases by slowing their progression. ^{1 3 5 6 7}

Who Is on the Research Team?

Radko Komers, MD, PhD

Principal Investigator

Travere Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for kids and teens with certain kidney diseases like FSGS or MCD, who have high levels of protein in their urine. They must be healthy enough in other ways (like liver function and blood pressure) to take part. Kids under a specific weight or those with certain medical conditions can't join.

Inclusion Criteria

For Population 2: You have a certain level of protein in your urine and meet specific diagnosis criteria.

Your urine protein levels are too high and meet specific diagnostic criteria.

I have FSGS confirmed by a kidney biopsy.

Exclusion Criteria

My kidney disease is due to FSGS or MCD.

I weigh less than 7.3 kg.

The subject has a history of allergic response to specific medications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sparsentan treatment to evaluate safety, efficacy, and pharmacokinetics over 108 weeks

108 weeks

Multiple visits including Day 1, Day 2, Week 12, and every 12 weeks thereafter

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 trial tests Sparsentan, an oral medication given once daily to see if it's safe, works well, and is tolerable over a period of 108 weeks. It specifically looks at how the drug affects the amount of protein in the urine among young patients.

How Is the Trial Designed?

Group I: Population 3: IgAN Experimental Treatment 1 Intervention

Subjects with kidney biopsy-confirmed IgAN

Group II: Population 2: IgAN, IgAV, or AS Experimental Treatment 1 Intervention

Subjects with kidney biopsy-confirmed immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), or Alport syndrome (AS)

Group III: Population 1: FSGS and/or MCD Experimental Treatment 1 Intervention

Subjects with selected proteinuric glomerular diseases associated with FSGS and MCD histological patterns

Sparsentan is already approved in United States, European Union for the following indications:

Approved in United States as Filspari for:

• To reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression
• To slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression

Approved in European Union as Filspari for:

• Treatment of adults with primary immunoglobulin A nephropathy (IgAN)

Who Is Running the Clinical Trial?

Travere Therapeutics, Inc.

Lead Sponsor

Trials

23

Recruited

103,000+

Published Research Related to This Trial

In a phase 3 trial involving 406 patients with IgA nephropathy, sparsentan significantly reduced proteinuria by 40% compared to irbesartan over 110 weeks, indicating its efficacy in managing kidney disease.

Sparsentan also demonstrated a slower decline in kidney function (eGFR) compared to irbesartan, suggesting it may help preserve kidney health without introducing new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Rovin, BH., Barratt, J., Heerspink, HJL., et al.[2023]

In a phase 3 trial involving 404 adults with IgA nephropathy, sparsentan significantly reduced proteinuria by 49.8% compared to a 15.1% reduction with irbesartan, indicating its superior efficacy in managing this condition.

The safety profile of sparsentan was comparable to irbesartan, with no severe adverse events reported, suggesting it is a safe treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Heerspink, HJL., Radhakrishnan, J., Alpers, CE., et al.[2023]

Sparsentan (FILSPARI™) is an oral medication that acts as a dual endothelin and angiotensin receptor antagonist, specifically developed for treating IgA nephropathy and FSGS.

In February 2023, sparsentan received accelerated approval in the USA for its effectiveness in reducing proteinuria in adults with primary IgA nephropathy, particularly those at risk of rapid disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sparsentan: First Approval. Syed, YY.[2023]

The DUPLEX study is a phase 3 clinical trial involving approximately 300 patients with focal segmental glomerulosclerosis (FSGS) that aims to evaluate the long-term efficacy and safety of sparsentan, a dual endothelin and angiotensin receptor blocker, over 108 weeks.

Sparsentan will be compared to irbesartan, focusing on its ability to reduce proteinuria and protect kidney function, with key outcomes including changes in glomerular filtration rate and urinary protein-to-creatinine ratios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis. Komers, R., Diva, U., Inrig, JK., et al.[2022]

Sparsentan, a dual endothelin angiotensin receptor antagonist, is being evaluated in the phase 3 PROTECT trial for its efficacy and safety in adults with IgA nephropathy (IgAN) and significant proteinuria, involving 404 patients from diverse regions including Europe, Asia Pacific, and North America.

The trial aims to assess sparsentan against irbesartan in patients who have not responded adequately to maximum doses of ACE inhibitors or ARBs, providing insights into its potential benefits for patients at high risk of kidney failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study. Barratt, J., Rovin, B., Wong, MG., et al.[2023]

The DUET study is evaluating the efficacy and safety of sparsentan, a dual-acting angiotensin receptor blocker and endothelin Type A receptor antagonist, in reducing proteinuria in patients with primary focal segmental glomerulosclerosis (FSGS) over an 8-week period compared to irbesartan, a standard ARB.

This phase 2 trial involves patients aged 8 to 75 years and aims to determine if sparsentan can significantly lower the urinary protein-to-creatinine ratio, potentially offering a new treatment option for a condition with currently no FDA-approved therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Sparsentan Compared With Irbesartan in Patients With Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET). Komers, R., Gipson, DS., Nelson, P., et al.[2022]

In a phase 3 trial involving 371 patients with focal segmental glomerulosclerosis (FSGS), sparsentan demonstrated a significantly higher rate of partial remission of proteinuria (42.0%) compared to irbesartan (26.0%) at 36 weeks, indicating its efficacy in reducing protein levels in urine.

Despite the greater reduction in proteinuria with sparsentan, there were no significant differences in kidney function (eGFR slope) between sparsentan and irbesartan over 108 weeks, suggesting that while sparsentan is effective for proteinuria, it may not lead to improved long-term kidney function compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. Rheault, MN., Alpers, CE., Barratt, J., et al.[2023]

Citations

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

Sparsentan versus Irbesartan in Focal Segmental ... In an 8-week, phase 2 trial, sparsentan, a dual endothelin–angiotensin receptor antagonist, reduced proteinuria in patients with FSGS.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07219121

Sparsentan in Posttransplant Immunoglobulin A ... This is a 46-week, open-label, multicenter, single-group Phase 4 study to determine the safety and efficacy of sparsentan for the treatment ...

3. ir.travere.com ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-to-Present-New-FILSPARI-sparsentan-Data-at-the-National-Kidney-Foundation-Spring-Clinical-Meetings-2025/default.aspx

News Late-breaking oral presentation details partial and complete proteinuria remission data from the DUPLEX Study of FILSPARI in FSGS.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01613118

Study Details | NCT01613118 | Randomized, Double-Blind ... Primary efficacy objective is to determine the change in UP/C in FSGS patients receiving RE-021 (Sparsentan) from baseline to 8 weeks over a range of dose ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11145552/

Sparsentan for Focal Segmental Glomerulosclerosis in the ... The proportions of patients reaching a confirmed 40% reduction in eGFR from the first sparsentan dose (consecutive eGFR results at least 28 days apart) or KF ( ...

6. ir.travere.com ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-to-Present-Abstracts-at-American-Society-of-Nephrology-ASN-Kidney-Week-2025/default.aspx

News Data presentations highlight biomarker and cardiovascular safety data from SPARTAN Study of FILSPARI in patients with IgAN. SAN DIEGO ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37706310/

A First-in-Class Dual Endothelin and Angiotensin II ... Sparsentan reduces proteinuria in IgAN and FSGS, and has expedited approval by the FDA for IgAN in patients at risk of rapid disease progression.