Sparsentan for Proteinuric Kidney Disease

(EPPIK Trial)

Recruiting at 41 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

Trial Summary

What is the purpose of this trial?

This trial is testing sparsentan, a daily oral medication, in children with specific kidney diseases that cause high protein levels in urine. The goal is to see if it is safe and effective. Sparsentan helps by reducing protein leakage into the urine, which can protect the kidneys.

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.

What data supports the effectiveness of the drug Sparsentan for proteinuric kidney disease?

Sparsentan has been shown to reduce proteinuria (excess protein in urine) in patients with IgA nephropathy and focal segmental glomerulosclerosis (FSGS), which are types of kidney diseases. It was approved in the USA for reducing proteinuria in adults with IgA nephropathy, and studies have shown it to be more effective than irbesartan, another drug used for similar conditions. ^{1 2 3 4 5}

Is Sparsentan safe for humans?

Sparsentan has been studied for safety in clinical trials for kidney diseases like IgA nephropathy and focal segmental glomerulosclerosis (FSGS). These studies suggest it has a favorable safety profile, meaning it is generally safe for humans. ^{1 2 3 5 6}

How is the drug Sparsentan different from other treatments for proteinuric kidney disease?

Sparsentan is unique because it is a dual endothelin angiotensin receptor antagonist, meaning it blocks two pathways that contribute to kidney damage, unlike other treatments that typically target only one. It is also non-immunosuppressive, which means it doesn't weaken the immune system, and is taken orally. ^{1 2 3 5 7}

Research Team

Radko Komers, MD, PhD

Principal Investigator

Travere Therapeutics, Inc.

Eligibility Criteria

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 am under 18 years old and older than 1 year.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Sparsentan: First Approval. [2023]

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. [2023]

5. United States 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). [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study. [2023]