Sparsentan for IgA Nephropathy

(PROTECT Trial)

Not currently recruiting at 175 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Travere Therapeutics, Inc.

Must be taking: ACEI, ARB

Must not be taking: Systemic immunosuppressives, Corticosteroids

Disqualifiers: CKD, Heart failure, Hepatobiliary 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: 110 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a new treatment, sparsentan, works for people with IgA nephropathy, a kidney disease that causes inflammation and can lead to kidney damage, over about two years. It compares sparsentan to irbesartan, a medication already used for this condition. Some participants might also try a combination of sparsentan and dapagliflozin, another medication, for a shorter period. People diagnosed with IgA nephropathy, who have a certain level of protein in their urine, and are on a steady dose of specific blood pressure medications might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of ACEI (angiotensin-converting enzyme inhibitor) and/or ARB (angiotensin receptor blocker) therapy for at least 12 weeks before screening. You must be willing to change these medications if needed, but the protocol does not specify stopping other current medications.

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

Research has shown that sparsentan is generally safe for treating IgA nephropathy, a type of kidney disease. Common side effects include high potassium levels, low blood pressure, swelling, dizziness, and anemia. Importantly, researchers have found no major safety issues.

When combined with dapagliflozin (another medication), sparsentan is also considered safe. This combination can help lower protein levels in urine, benefiting kidney health.

Sparsentan has already received approval for adults with IgA nephropathy, indicating it has passed important safety tests for this condition. Overall, sparsentan and its combination with dapagliflozin appear well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sparsentan for IgA nephropathy because it combines two mechanisms of action: it blocks both angiotensin II and endothelin, which are proteins that can contribute to kidney damage. Unlike standard treatments like ACE inhibitors or ARBs, which only target one pathway, sparsentan aims to offer a more comprehensive approach to protect kidney function. Additionally, there's a sub-study combining sparsentan with dapagliflozin, an SGLT2 inhibitor, which could offer further benefits by reducing proteinuria and improving kidney health. This dual-targeting strategy represents a novel approach in managing IgA nephropathy, potentially offering better outcomes for patients.

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

Research has shown that sparsentan, one of the treatments in this trial, effectively treats IgA nephropathy (IgAN), a kidney disease. Studies have found that it can reduce protein in urine by up to 62% after 14 weeks. This reduction is important because less protein in urine often indicates slower kidney damage. In this trial, sparsentan is compared to irbesartan, another treatment option, and previous studies have shown sparsentan to be more effective in slowing kidney function decline. Additionally, using sparsentan with dapagliflozin, as explored in a sub-study arm, has further improved results in reducing protein in urine. These findings suggest that sparsentan, whether used alone or with dapagliflozin, may offer strong kidney protection for patients with IgAN. ^{1 2 3 5 6}

Who Is on the Research Team?

Radko Komers, MD, PhD

Principal Investigator

Travere Therapeutics, Inc.

Are You a Good Fit for This Trial?

Adults with IgA Nephropathy (kidney disease) who've completed a previous study phase, have stable blood pressure and kidney function, are on certain blood pressure meds, and agree to contraception can join. Excluded if they're pregnant/breastfeeding, drug/alcohol disorder, severe liver issues, high potassium levels or taking disallowed medications.

Inclusion Criteria

I am willing to change my blood pressure medications if needed.

Did not permanently discontinue study medication during the double-blind period

I have been on a stable dose of ACEI or ARB for at least 12 weeks.

Exclusion Criteria

I am currently pregnant or breastfeeding.

I do not have jaundice, hepatitis, or liver disease, and my liver tests are normal.

I couldn't start or had to stop RAAS inhibitors between Week 110 and 114.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sparsentan or irbesartan in a double-blind manner, with dose adjustments after 2 weeks, continuing treatment to Week 110

110 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue treatment with sparsentan for up to 156 weeks, with an optional sub-study involving dapagliflozin

156 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Irbesartan
• Sparsentan

Trial Overview The trial is testing the long-term kidney protection of Sparsentan compared to an angiotensin receptor blocker in patients with IgA Nephropathy over approximately two years. Participants will either continue with their current treatment or switch to Sparsentan.

How Is the Trial Designed?

Group I: sparsentan (Sub Study) Experimental Treatment 1 Intervention

OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.

Group II: sparsentan Experimental Treatment 1 Intervention

Double-blind: Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400- mg and continue treatment to Week 110.

Group III: dapagliflozin + sparsentan (Sub study) Experimental Treatment 2 Interventions

OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.

Group IV: irbesartan Active Control 1 Intervention

Double-blind: Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.

Who Is Running the Clinical Trial?

Travere Therapeutics, Inc.

Lead Sponsor

Trials

23

Recruited

103,000+

Published Research Related to This Trial

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]

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]

Citations

1. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/profiles_of_iga_deposition_and_patterns_in_kidney.2429.aspx

Sparsentan (SPAR) in Combination with SGLT2 Inhibitors... One pt achieved complete remission of proteinuria (UPCR <0.3 g/g) after 3 mo of SPAR + SGLT2i tx. In all pts, proteinuria improved to a greater extent with SPAR ...

2. academic.oup.com academic.oup.com/ckj/article/18/1/sfae394/7915992

First real-world evidence of sparsentan efficacy in patients ... Sparsentan shows a significant impact on proteinuria, leading to a relative reduction of 62% in UPCR after 14 weeks and beyond, even in patients already ...

3. medicalaffairs.travere.com medicalaffairs.travere.com/posters/sparsentan-sglt2i-combination-igan-case-series/

Combining Sparsentan and SGLT2i in IgAN | Travere Medical ... Sparsentan is a non-immunosuppressive, Dual Endothelin Angiotensin Receptor Antagonist (DEARA) approved for use in adults with IgA ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-sparsentan-and-dapagliflozin-for-patients-with-immunoglobulin-a-nephropathy-igan/

Study on the Effectiveness and Safety of Sparsentan ... This clinical trial investigates the safety and efficacy of Sparsentan, alone or in combination with Dapagliflozin, in treating Immunoglobulin A Nephropathy ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10166729/

IgA Nephropathy Patient Baseline Characteristics in the ... In DUET, a phase 2 randomized controlled clinical trial, treatment with sparsentan significantly reduced proteinuria compared to the active control ARB ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03762850

NCT03762850 | A Study of the Effect and Safety ... Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 ...