Atrasentan for Kidney Disease

(AFFINITY Trial)

Recruiting at 71 trial locations

Overseen By Lesley Inker

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chinook Therapeutics U.S., Inc.

Must be taking: RAS inhibitors, SGLT2 inhibitors

Must not be taking: Systemic immunosuppressants

Disqualifiers: Other CKD, Transplant, Hypertension, Heart failure, Malignancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

103 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a pill called atrasentan that may help people with certain kidney diseases by reducing harmful protein levels in their urine. It targets patients whose kidney function is getting worse despite standard treatments. The goal is to see if this medication can protect their kidneys.

Do I need to stop my current medications to join the trial?

The trial requires that you continue taking a stable dose of certain medications, like RAS inhibitors for at least 12 weeks, and for some cohorts, a stable dose of SGLT2 inhibitors or immunosuppressants. The protocol does not specify stopping other medications, so it's best to discuss your current medications with the study team.

What safety data exists for Atrasentan in humans?

Atrasentan has been studied in patients with advanced prostate cancer, and some common side effects reported include swelling (peripheral edema), runny nose (rhinitis), headache, infections, difficulty breathing (dyspnea), and heart failure. ^{1 2 3 4 5}

How is the drug Atrasentan unique for treating kidney disease?

Atrasentan is unique for treating kidney disease because it is a selective endothelin-A receptor antagonist, which helps reduce proteinuria (excess protein in urine) and kidney damage by blocking the effects of endothelin-1, a substance that can harm the kidneys when produced in excess. This mechanism is different from other treatments that may not specifically target endothelin-1. ^{1 2 3 4 6}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults with certain kidney diseases (like IgA Nephropathy, FSGS, Alport Syndrome) who have protein in their urine and are at risk of worsening kidney function. Participants must meet specific criteria including age limits (18+ or 18-70 depending on the condition), a confirmed diagnosis through biopsy, stable blood filtration rates, and be on steady doses of certain diabetes or blood pressure medications.

Inclusion Criteria

I have been on a steady dose of an SGLT2 inhibitor for 3 months.

Your body mass index (BMI) is less than or equal to 40 kg/m2.

I have been on a stable dose of RAS inhibitor therapy for at least 12 weeks.

Exclusion Criteria

I have a chronic kidney condition not caused by my current kidney disease.

I have a significant history of liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 0.75 mg atrasentan QD for 52 weeks

52 weeks

Treatment Extension

Participants may continue treatment with oral atrasentan QD for up to an additional 84 weeks

84 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atrasentan

Trial Overview The AFFINITY Study is testing Atrasentan's effectiveness and safety in patients with different types of proteinuric glomerular diseases. It's an open-label phase 2 study which means everyone knows they're getting Atrasentan and it’s early in the drug testing process to see if it works well.

Participant Groups

Group I: Atrasentan 1.5 mg Experimental Treatment 1 Intervention

Once daily oral administration 1.5 mg atrasentan (FSGS cohorts only)

Group II: Atrasentan 0.75 mg Experimental Treatment 1 Intervention

Once daily oral administration of 0.75 mg atrasentan

Who Is Running the Clinical Trial?

Chinook Therapeutics U.S., Inc.

Lead Sponsor

Trials

2

Recruited

510+

Chinook Therapeutics, Inc.

Lead Sponsor

Trials

10

Recruited

1,100+

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Atrasentan, an oral anti-cancer drug targeting endothelin-A receptors, was studied in patients with advanced prostate cancer but did not show significant benefits in delaying disease progression compared to placebo in Phase II and III trials.

Patients treated with atrasentan experienced more adverse effects, including peripheral edema and heart failure, raising concerns about its safety profile in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrasentan for metastatic hormone refractory prostate cancer. Murphy, G.[2014]

In a study involving 809 men with metastatic hormone-refractory prostate cancer, atrasentan did not significantly reduce the risk of disease progression compared to placebo, indicating limited efficacy in delaying cancer advancement.

However, atrasentan treatment was associated with a significant delay in the progression of bone alkaline phosphatase (BAP) levels, suggesting some biological effects, and it was generally well-tolerated with manageable side effects like headache and peripheral edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Carducci, MA., Saad, F., Abrahamsson, PA., et al.[2022]

Atrasentan is a selective endothelin ET(A) receptor antagonist being developed for the treatment of various cancers, particularly prostate cancer, and is currently in phase III trials.

The drug has received Fast Track status, which allows for expedited review, and the company plans to file for approval for prostate cancer treatment by late 2003.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrasentan Abbott. Norman, P.[2018]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Atrasentan for metastatic hormone refractory prostate cancer. [2014]

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

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Atrasentan Abbott. [2018]

4. England pubmed.ncbi.nlm.nih.gov

High-throughput determination of atrasentan in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. [2019]

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

Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800). [2021]

6. England pubmed.ncbi.nlm.nih.gov

Atrasentan for the treatment of diabetic nephropathy. [2018]