What is the mechanism of action of this treatment?

The most common treatments for Immunoglobulin A Nephropathy (IgAN) include endothelin receptor antagonists like Atrasentan, ACE inhibitors, and ARBs. Endothelin receptor antagonists work by blocking the effects of endothelin-1, a potent vasoconstrictor that contributes to kidney inflammation and fibrosis. ACE inhibitors and ARBs reduce proteinuria and blood pressure by inhibiting the renin-angiotensin-aldosterone system, which helps to protect kidney function. These treatments are essential for IgAN patients as they help to slow disease progression, reduce proteinuria, and preserve kidney function.

What side effects are associated with this type of intervention?

Common treatments for Immunoglobulin A Nephropathy (IgAN) include Endothelin Receptor Antagonists (ERAs) like Atrasentan, glucocorticoids, angiotensin inhibitors, and SGLT2 inhibitors. ERAs can cause fluid retention, nasal congestion, and headaches. Glucocorticoids are associated with serious adverse events such as severe infections and Cushingoid features. Angiotensin inhibitors may lead to hyperkalemia and renal dysfunction. SGLT2 inhibitors can cause genital infections and dehydration. Each treatment has a unique side effect profile that should be considered when managing IgAN.

What prior FDA approvals exist?

The FDA has approved several treatments for IgA Nephropathy, primarily focusing on managing symptoms and slowing disease progression. These include angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) to reduce proteinuria and control blood pressure. While Atrasentan, an Endothelin Receptor Antagonist, is being studied for its efficacy in treating IgA Nephropathy, similar drugs like sparsentan, which also targets endothelin receptors, are under investigation but not yet FDA-approved specifically for IgA Nephropathy.

What other types of research exist?

Promising novel alternatives to Atrasentan for IgA Nephropathy patients include the use of SGLT2 inhibitors, which have shown efficacy in combination with standard care in clinical trials. Additionally, monoclonal antibodies like Rituximab and immunosuppressive agents such as Mycophenolate Mofetil have been used successfully in treating glomerular diseases and may offer potential benefits for IgAN patients.

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Endothelin Receptor Antagonist

Atrasentan for IgA Nephropathy (ASSIST Trial)

Phase 2

Recruiting

Research Sponsored by Chinook Therapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Subjects aged 18 and older at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures

eGFR of at least 30 mL/min/1.73 m2 at screening based on the CKD-EPI equation

Must not have

Current diagnosis with another chronic kidney disease, including diabetic kidney disease

Use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and 24 weeks or approximately 6 months

Awards & highlights

Summary

This trial is testing atrasentan, a medication for people with IgA nephropathy (IgAN) who are already on standard treatments. It works by blocking pathways that cause kidney damage, aiming to lower protein levels in the urine. Atrasentan has been previously tested for its effects on albuminuria reduction in patients with type 2 diabetes and nephropathy.

Who is the study for?

Adults with IgA Nephropathy who have significant protein in their urine can join this trial. They must be on stable doses of specific kidney medications and agree to use effective contraception. Excluded are those with heart failure, other chronic kidney diseases, recent cancer (except certain skin or cervical cancers), blood pressure issues, severe liver disease, organ transplants, or recent immunosuppressant use.

What is being tested?

The ASSIST study is testing Atrasentan against a placebo in patients with IgA Nephropathy already taking standard care and an SGLT2 inhibitor. It's a phase 2 trial where participants will switch between the drug and placebo at different times without knowing which one they're taking.

What are the potential side effects?

Possible side effects of Atrasentan may include fluid retention leading to swelling or weight gain, nasal congestion, heart problems like irregular heartbeat or chest pain, and gastrointestinal symptoms such as nausea.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years or older and have signed the consent form.

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My kidney function is adequate, with an eGFR of at least 30.

Exclusion Criteria

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

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I have a chronic kidney condition, such as diabetic kidney disease.

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I have not taken immunosuppressants like steroids for more than 2 weeks in the last 3 months.

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My hemoglobin is below 9 g/dL or I've had a blood transfusion for anemia in the last 3 months.

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I have a history of heart failure or was hospitalized for fluid buildup.

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I do not plan to father a child or donate sperm during the study.

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I have had a kidney or other organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and 24 weeks or approximately 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and 24 weeks or approximately 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and 24 weeks or approximately 6 months 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 From Baseline in Proteinuria at Week 12 in Both Treatment Periods 1 and 2

Secondary study objectives

Change From Baseline in Proteinuria at Week 24 in Treatment Periods 2

Number of Subjects With Adverse Events (AEs)

Plasma Concentration of Atrasentan

Trial Design

2Treatment groups

Experimental Treatment

Group I: Sequence BAExperimental Treatment2 Interventions

Once daily oral administration of placebo for 12 weeks (Period B) followed by once daily oral administration of 0.75 mg atrasentan for 24 weeks (Period A)

Group II: Sequence ABExperimental Treatment2 Interventions

Once daily oral administration of 0.75 mg atrasentan for 12 weeks (Period A) followed by once daily oral administration of placebo for 24 weeks (Period B)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atrasentan

2011

Completed Phase 3

~420

Placebo

1995

Completed Phase 3

~2670

0 / 8Eligibility 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 Immunoglobulin A Nephropathy (IgAN) include endothelin receptor antagonists like Atrasentan, ACE inhibitors, and ARBs. Endothelin receptor antagonists work by blocking the effects of endothelin-1, a potent vasoconstrictor that contributes to kidney inflammation and fibrosis. ACE inhibitors and ARBs reduce proteinuria and blood pressure by inhibiting the renin-angiotensin-aldosterone system, which helps to protect kidney function. These treatments are essential for IgAN patients as they help to slow disease progression, reduce proteinuria, and preserve kidney function.