Sparsentan for Focal Segmental Glomerulosclerosis

(DUPLEX Trial)

Not currently recruiting at 220 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Travere Therapeutics, Inc.

Must not be taking: Rituximab, Cyclophosphamide, Abatacept

Disqualifiers: Diabetes, Heart disease, Liver disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 108 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug sparsentan protects the kidneys in people with focal segmental glomerulosclerosis (FSGS), a condition that causes kidney scarring. Participants will receive either sparsentan or irbesartan (an angiotensin receptor blocker) to compare their effectiveness. The trial targets individuals diagnosed with FSGS through a biopsy or genetic test and who meet specific kidney function criteria. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on certain immunosuppressive drugs, the dosage must be stable before joining. Also, you cannot have taken rituximab, cyclophosphamide, or abatacept within 3 months before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sparsentan has been consistently safe in previous studies. Long-term use of sparsentan led to a lasting decrease in protein in the urine, without major safety issues. In a study lasting 108 weeks, researchers compared sparsentan to irbesartan, and the results supported its overall safety for patients with focal segmental glomerulosclerosis (FSGS).

Irbesartan, the drug used for comparison, is a well-known blood pressure medication that is generally well-tolerated. Both sparsentan and irbesartan were taken as daily pills, with sparsentan showing effective results in earlier research without significant side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for FSGS?

Sparsentan is unique because it combines two mechanisms of action to target focal segmental glomerulosclerosis (FSGS). Unlike standard treatments like irbesartan, which primarily block angiotensin II to reduce blood pressure, sparsentan also blocks endothelin, a protein that can contribute to kidney damage. Researchers are excited about sparsentan's potential to more effectively protect kidney function and slow disease progression by addressing these two pathways simultaneously.

What evidence suggests that this trial's treatments could be effective for FSGS?

Research has shown that sparsentan, one of the treatments in this trial, holds promise for treating focal segmental glomerulosclerosis (FSGS), a kidney condition. Studies have demonstrated that sparsentan significantly lowers proteinuria, reducing excess protein in the urine—a primary symptom of FSGS. An 8-week study found that sparsentan reduced proteinuria more effectively than irbesartan, the other treatment option in this trial. Specifically, about 28.1% of patients using sparsentan experienced a partial improvement in proteinuria, highlighting its potential effectiveness. These findings suggest sparsentan could be a strong option for people with FSGS. ^{1 2 3 4 6}

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 individuals with primary or genetic FSGS, a kidney disease. Participants must be between 8-75 years old, weigh over 20 kg, and have certain levels of protein in their urine. Women who can bear children should agree to use reliable contraception methods. People with secondary FSGS, uncontrolled diabetes, significant liver disease, recent cancer (except some skin/cervical cancers), extreme obesity related to FSGS, drug abuse history or severe reactions to specific heart medications cannot join.

Inclusion Criteria

I have a confirmed diagnosis of FSGS through a biopsy or genetic test.

I am between 8 and 75 years old and weigh at least 20 kg.

You have a high level of protein in your urine.

Exclusion Criteria

My FSGS is caused by another health condition.

You had a bad reaction to drugs that work on the angiotensin system or endothelin system in the past.

I have taken rituximab, cyclophosphamide, or abatacept within the last 3 months, or my immunosuppressive medication dose has been stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

Patients require washout from renin-angiotensin-aldosterone system (RAAS) blockers, if applicable, prior to their first dose of study drug

2 weeks

Treatment

Participants receive either sparsentan or irbesartan in a double-blind manner

108 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with sparsentan long-term

What Are the Treatments Tested in This Trial?

Interventions

• Irbesartan
• Sparsentan

Trial Overview The study compares the long-term kidney protection effects of Sparsentan against Irbesartan in patients with FSGS. It aims to see if Sparsentan is better at preserving kidney function over time compared to the current treatment option.

How Is the Trial Designed?

Group I: sparsentan for double-blind and open-label extension Experimental Treatment 1 Intervention

Sparsentan will be administered as a single oral dose; an initial dose of 400 mg daily titrating up to a target dose of 800 mg, daily

Group II: Irbesartan Active Control 1 Intervention

Irbesartan will be administered as a single oral dose; an initial dose of 150 mg daily titrating up to a target dose of 300 mg, daily

Who Is Running the Clinical Trial?

Travere Therapeutics, Inc.

Lead Sponsor

Trials

23

Recruited

103,000+

Published Research Related to This Trial

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]

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]

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. 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 ...

2. ir.travere.com ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-Provides-Update-on-FDA-Advisory-Committee-Meeting-for-FILSPARI-sparsentan-in-FSGS/default.aspx

Travere Therapeutics Provides Update on FDA Advisory ... While DUPLEX achieved its pre-specified interim FSGS partial remission of proteinuria (FPRE) endpoint with statistical significance at 36 weeks, ...

3. 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.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38831932/

Sparsentan for Focal Segmental Glomerulosclerosis in the ... Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

5. renalandurologynews.com renalandurologynews.com/news/sparsentan-under-review-for-focal-segmental-glomerulosclerosis/

Sparsentan Under Review for Focal Segmental ... Results also showed 28.1% of patients treated with sparsentan achieved the FSGS partial remission of proteinuria endpoint (UP/C ≤1.5 g/g and >40 ...

6. 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 ...