What is the mechanism of action of this treatment?

The most common treatments for IgA Nephropathy (IgAN) include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which reduce proteinuria and slow disease progression by inhibiting the renin-angiotensin system, thereby lowering blood pressure and reducing glomerular pressure. Endothelin receptor antagonists, like Sparsentan, target endothelin-1, a molecule that contributes to kidney damage through vasoconstriction, inflammation, and fibrosis. By blocking both endothelin and angiotensin receptors, Sparsentan may offer enhanced protection against kidney damage. Corticosteroids and immunosuppressants are also used, particularly in high-risk patients, to reduce inflammation and immune-mediated damage. Understanding these mechanisms is crucial for IgAN patients as it helps tailor treatment strategies to effectively manage the disease and prevent progression to kidney failure.

What side effects are associated with this type of intervention?

Common treatments for IgA Nephropathy include ACE inhibitors, ARBs, and SGLT2 inhibitors, which are often used to manage proteinuria and blood pressure. Side effects of ACE inhibitors and ARBs can include hyperkalemia, hypotension, and renal function deterioration. SGLT2 inhibitors may cause urinary tract infections, genital infections, and dehydration. Sparsentan, being a dual endothelin receptor and angiotensin II receptor antagonist, may share similar side effects, including potential risks of hypotension, hyperkalemia, and renal impairment.

What prior FDA approvals exist?

The FDA has approved several treatments for IgA Nephropathy, primarily focusing on reducing proteinuria and slowing disease progression. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are commonly used and have shown efficacy in reducing proteinuria and preserving kidney function. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have also been recommended for patients with proteinuric chronic kidney disease, including IgA Nephropathy, due to their kidney-protective effects. While Sparsentan, a dual endothelin receptor and angiotensin II receptor antagonist, is currently under investigation, it represents a novel approach that combines the benefits of both endothelin receptor antagonism and angiotensin II receptor blockade.

What other types of research exist?

Promising alternatives to Sparsentan for IgA Nephropathy patients include: 1) SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) which have shown cardiorenal benefits and reduction in albuminuria; 2) Immunosuppressive therapies such as mycophenolate mofetil (MMF) combined with glucocorticoids, especially in patients with high macrophage infiltration; 3) Endothelin receptor antagonists like atrasentan, which may be used in combination with SGLT2 inhibitors to enhance kidney protection and reduce fluid retention.

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Angiotensin II Receptor Blocker and Endothelin Receptor Antagonist

Sparsentan for IgA Nephropathy (SPARTACUS Trial)

Phase 2

Waitlist Available

Research Sponsored by Travere Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Aged ≥18 years at the time of signing the informed consent.

Be older than 18 years old

Must not have

IgAN secondary to another condition or immunoglobulin A (IgA) vasculitis.

Taking high dose (defined as >10 mg/day prednisone) or any other systemic immunosuppressive medications within 12 weeks prior to screening.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 24

Awards & highlights

No Placebo-Only Group

Summary

This trial will test sparsentan, a drug for people with IgAN whose condition is worsening despite other treatments. It works by blocking proteins that can damage the kidneys. The study will check if sparsentan can safely help these patients and protect kidney function.

Who is the study for?

Adults over 18 with IgA Nephropathy (IgAN), a kidney disease, can join this trial if they've had a biopsy confirming their condition. They must have been on stable doses of specific blood pressure medications (ACEI/ARB) and SGLT2 inhibitors for at least 12 weeks. Their urine test should show protein levels above a certain threshold, and their kidneys must be functioning above a set level. People who've had organ transplants (except corneal), severe heart or liver issues, secondary IgAN, or recent high-dose steroids cannot participate.

What is being tested?

The study is testing the safety and effects of Sparsentan in combination with SGLT2 inhibitors in people with IgAN at risk of progressing to kidney failure despite current treatments. It's an open-label Phase 2 trial lasting for about half a year where all participants will receive the same treatment without any comparison group.

What are the potential side effects?

While not explicitly listed here, potential side effects may include those commonly associated with new medications such as headaches, nausea, high blood pressure changes due to Sparsentan's action on blood vessels, and possible interactions with existing medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My IgA nephropathy is caused by another condition or I have IgA vasculitis.

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I have not taken high doses of prednisone or any immunosuppressants in the last 12 weeks.

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I have not had any organ transplants except for a corneal transplant.

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I have a history of heart, liver, or significant cardiovascular disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in urine albumin-creatinine ratio (UA/C) at Week 24

Secondary study objectives

30% and 50% reduction from baseline in UA/C at Week 24

Blood pressure (BP) at each visit

Estimated glomerular filtration rate (eGFR) at each visit

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: sparsentanExperimental Treatment1 Intervention

Sparsentan will be administered daily as a 200-mg oral tablet. The goal is to titrate from the initial dose of 200 mg (Day 1) to the target dose of 400 mg at Week 2.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sparsentan

2023

Completed Phase 2

~50

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for IgA Nephropathy (IgAN) include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which reduce proteinuria and slow disease progression by inhibiting the renin-angiotensin system, thereby lowering blood pressure and reducing glomerular pressure. Endothelin receptor antagonists, like Sparsentan, target endothelin-1, a molecule that contributes to kidney damage through vasoconstriction, inflammation, and fibrosis. By blocking both endothelin and angiotensin receptors, Sparsentan may offer enhanced protection against kidney damage. Corticosteroids and immunosuppressants are also used, particularly in high-risk patients, to reduce inflammation and immune-mediated damage. Understanding these mechanisms is crucial for IgAN patients as it helps tailor treatment strategies to effectively manage the disease and prevent progression to kidney failure.

Quantitative Comparison of the Clinical Efficacy of 6 Classes Drugs for IgA Nephropathy: A Model-Based Meta-Analysis of Drugs for Clinical Treatments.Comparison of the effects of valsartan plus activated vitamin D versus valsartan alone in IgA nephropathy with moderate proteinuria.Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial.