Atrasentan for Kidney Disease

(AFFINITY Trial)

Not currently recruiting at 75 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, atrasentan, to determine its effectiveness in treating certain kidney diseases that cause proteinuria (excess protein in urine) and risk worsening kidney function. The trial includes two treatment groups, each receiving different daily doses of atrasentan. Suitable participants have conditions such as IgA nephropathy, FSGS, Alport syndrome, or diabetic kidney disease and are already on stable medication for these issues. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that atrasentan is likely to be safe for humans?

Research has shown that atrasentan is generally safe for people. In one study, patients taking atrasentan for kidney problems experienced lower blood pressure and improved blood sugar and cholesterol levels, suggesting its safety. Another study found that combining atrasentan with losartan (a medicine for high blood pressure) was as safe as using losartan alone, indicating no additional safety concerns. Overall, the evidence supports the safety of atrasentan, but researchers will continue monitoring during trials to ensure everyone's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Unlike the standard treatments for kidney disease, which often include medications like ACE inhibitors and ARBs that primarily manage symptoms, atrasentan offers a new approach by targeting the endothelin pathway specifically. This pathway is involved in kidney damage, so blocking it with atrasentan could help slow down or even prevent further kidney decline. Researchers are particularly excited because atrasentan shows promise in reducing proteinuria, a key marker of kidney disease progression, which could lead to better long-term outcomes for patients.

What evidence suggests that atrasentan might be an effective treatment for kidney disease?

Research has shown that atrasentan may help treat kidney disease by reducing the amount of protein in urine, a major issue in kidney problems. Studies have found that atrasentan can lower this excess protein and improve kidney health markers without greatly affecting blood pressure. In this trial, participants will receive either 0.75 mg or 1.5 mg of atrasentan. For patients with diabetic kidney disease, long-term use of atrasentan has been linked to better kidney and heart health. It also helps protect the heart, which is important for people with kidney issues. Overall, evidence suggests that atrasentan could be helpful in managing kidney disease. ^{3 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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.

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

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

Exclusion Criteria

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

I have a significant history of liver problems.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2025/219208Orig1s000IntegratedR.pdf

219208Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov

Trial Outcomes for Kidney Failure: 2020” (Levin et al. 2020). Reference ID: 5563590. Page 194. NDA 219208. Vanrafia (atrasentan). 181.

2.

access.portico.org

access.portico.org/Portico/show?viewFile=pdf&auId=pjbf78x6z3w

Atrasentan

ABT-627 has displayed promising results suggesting that it may be effective in the treatment of pulmonary hypertension (17), essential hypertension. (18, 19), ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC1751871/

Cardioprotective effects of atrasentan, an endothelin-A ...

Atrasentan reduced diabetic urine flow, proteinuria and plasma creatinine levels, but creatinine clearance was not significantly altered. These results suggest ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01858532

Study Of Diabetic Nephropathy With Atrasentan (SONAR)

Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4361570/

Endothelin A Receptor Antagonist, Atrasentan, Attenuates ...

At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04573920

Atrasentan in Patients With Proteinuric Glomerular Diseases

The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04573478

NCT04573478 | Atrasentan in Patients With IgA Nephropathy

The ALIGN Study is a phase 3, double-blind, placebo-controlled study to compare the efficacy and safety of atrasentan to placebo in patients with IgA ...

8.

novartis.com

novartis.com/news/media-releases/novartis-atrasentan-phase-iii-data-show-clinically-meaningful-proteinuria-reduction-further-advancing-companys-iga-nephropathy-igan-portfolio

Novartis atrasentan Phase III data show clinically ...

Novartis atrasentan Phase III data show clinically meaningful proteinuria reduction further advancing company's IgA nephropathy (IgAN) portfolio.

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2675066/

Efficacy and Safety of Atrasentan in Patients With ...

In conclusion, 6 months of treatment with atrasentan results in a reduction of blood pressure and improvement in glucose and lipid metabolism. These findings ...