Atrasentan for IgA Nephropathy

(ASSIST Trial)

Not currently recruiting at 39 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chinook Therapeutics, Inc.

Must be taking: RAS inhibitors, SGLT2 inhibitors

Must not be taking: Systemic immunosuppressants

Disqualifiers: Chronic kidney disease, Transplantation, Hypertension, Heart failure, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called atrasentan to determine its potential benefits for people with IgA nephropathy, a kidney disease that can cause kidney damage. The study compares atrasentan to a placebo (a pill with no active drug) to assess its safety and effectiveness. Participants must have IgA nephropathy confirmed by a kidney biopsy and be on a stable dose of certain kidney medications. Those managing IgA nephropathy with stable medication might find this trial suitable. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of a RAS inhibitor and an SGLT2 inhibitor before joining. If you are taking other investigational or certain immunosuppressive medications, a washout period (time without taking these medications) may be required.

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

Research has shown that atrasentan is being tested for safety in treating IgA nephropathy, a kidney condition. In one study, 11.2% of patients taking atrasentan experienced fluid retention, compared to 8.2% in the placebo group, but this did not cause any serious problems. Another review found that combining atrasentan with losartan, a common blood pressure medicine, is as safe as using losartan alone.

Since this trial is in an early stage, the treatment has been tested in people, but more information about its safety is needed. Overall, current findings suggest that atrasentan is generally well-tolerated, though monitoring for fluid retention remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IgA nephropathy?

Researchers are excited about atrasentan for IgA nephropathy because, unlike current treatments that primarily focus on controlling symptoms or reducing protein in urine, atrasentan directly targets the endothelin pathway. This pathway is involved in kidney inflammation and fibrosis, making atrasentan a potential game-changer in addressing the disease's root cause. Additionally, atrasentan is taken orally once daily, which could improve patient convenience and adherence compared to more complicated regimens.

What evidence suggests that atrasentan might be an effective treatment for IgA nephropathy?

Research has shown that atrasentan may help treat IgA nephropathy (IgAN). One study found that patients taking atrasentan had less protein in their urine, a key sign of kidney damage. This suggests that atrasentan might help protect kidney function in people with IgAN. In this trial, participants will receive atrasentan in one of the treatment sequences to further evaluate its effects. However, whether atrasentan can slow the worsening of kidney function over time in these patients remains unclear. Overall, these early results are promising for those considering joining a trial. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have been on a stable, high dose of blood pressure medication for at least 12 weeks.

Your kidney function, measured by eGFR, must be at least 30 mL/min/1.73 m2 before the study starts.

You need to have more than 0.5 grams of protein in your urine in a day.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Subjects not on background SGLT2i therapy undergo an 8-week run-in period with an SGLT2i

8 weeks

Treatment Period A

Participants receive 0.75 mg atrasentan once daily for 12 weeks

12 weeks

Visits at Weeks 2, 6, and 12

Washout

A 12-week washout period between treatment periods

12 weeks

Treatment Period B

Participants receive placebo once daily for 24 weeks

24 weeks

Visits at Weeks 2, 6, 12, and 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atrasentan
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Sequence BA Experimental Treatment 2 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 AB Experimental Treatment 2 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)

Who Is Running the Clinical Trial?

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

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 of 89 subjects with diabetic nephropathy, the endothelin A receptor antagonist atrasentan significantly reduced albuminuria at doses of 0.75 mg and 1.75 mg compared to placebo, indicating its efficacy in managing this condition.

While atrasentan was generally safe, higher doses (1.75 mg) were associated with increased rates of peripheral edema, suggesting that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of atrasentan to renin-angiotensin system blockade reduces albuminuria in diabetic nephropathy. Kohan, DE., Pritchett, Y., Molitch, M., 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]

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]

In a study of 211 patients with type 2 diabetic nephropathy, the endothelin A receptor antagonist atrasentan significantly reduced urine albumin/creatinine ratios by 35% and 38% at doses of 0.75 mg and 1.25 mg, respectively, indicating its efficacy in lowering albuminuria when used alongside RAS inhibitors.

Atrasentan also led to improvements in blood pressure and lipid levels, with manageable side effects, although higher doses were associated with increased weight and a reduction in hemoglobin, and some patients discontinued treatment due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy. de Zeeuw, D., Coll, B., Andress, D., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04573478

NCT04573478 | Atrasentan in Patients With IgA Nephropathy Approximately 320 patients with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39460694/

Atrasentan in Patients with IgA Nephropathy Atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy.

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

219208Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov Given the currently available data on the efficacy and safety of atrasentan and the intent of the ... Reduction as a Surrogate End Point in Trials ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05834738

Study Details | NCT05834738 | Randomized, Double-blind, ... The primary objective of the study is to evaluate the efficacy of atrasentan vs. placebo while on background therapy with SGLT2i. Subjects will have safety and ...

5. researchgate.net researchgate.net/publication/394289335_Atrasentan_First_Approval

Atrasentan: First Approval It has not been established whether atrasentan slows kidney function decline in patients with IgAN. This article summarizes the milestones in the development of ...

6. 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.