Atrasentan for IgA Nephropathy

(ASSIST Trial)

Recruiting at 34 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

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 atrasentan safe for human use?

Atrasentan has been studied for various conditions, including prostate cancer and diabetic nephropathy. Common side effects include peripheral edema (swelling), rhinitis (runny nose), headache, and heart failure. In diabetic nephropathy studies, it was generally safe but associated with fluid retention, especially at higher doses. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Atrasentan (Endothelin Receptor Antagonist)
• Placebo (Drug)

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.

Participant Groups

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

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]

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]

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

The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy. [2022]

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

Addition of atrasentan to renin-angiotensin system blockade reduces albuminuria in diabetic nephropathy. [2022]