Sparsentan for Focal Segmental Glomerulosclerosis

(DUPLEX Trial)

Recruiting at 198 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

371 Participants Needed

Trial Summary

What is the purpose of this trial?

To determine the long-term nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with primary and genetic focal segmental glomerulosclerosis (FSGS).

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.

What data supports the effectiveness of the drug Sparsentan for treating Focal Segmental Glomerulosclerosis?

Sparsentan has been shown to reduce proteinuria (excess protein in urine) in patients with Focal Segmental Glomerulosclerosis (FSGS) in an 8-week phase 2 trial, indicating its potential effectiveness for this condition. ^{1 2 3 4 5}

Is sparsentan safe for humans?

Sparsentan has been studied for safety in patients with kidney conditions like IgA nephropathy and focal segmental glomerulosclerosis (FSGS). It has shown a favorable safety profile in trials, meaning it is generally safe for humans, but the long-term safety is still being evaluated. ^{1 2 4 5 6}

What makes the drug Sparsentan unique for treating focal segmental glomerulosclerosis (FSGS)?

Sparsentan is unique because it is a first-in-class drug that combines two actions in one molecule: it blocks both endothelin type A receptors and angiotensin II type 1 receptors, which helps reduce proteinuria (excess protein in urine) more effectively than treatments that target only one of these pathways. ^{1 2 4 5 6}

Research Team

Radko Komers, MD, PhD

Principal Investigator

Travere Therapeutics, Inc.

Eligibility Criteria

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 18 and 75 years old and weigh at least 20 kg.

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

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

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

Treatment Details

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.

Participant Groups

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+

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 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]

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]

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]

References

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

Sparsentan: First Approval. [2023]

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

Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. [2023]

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

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS. [2023]

4. 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]

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]