Atrasentan for IgA Nephropathy

(ALIGN Trial)

Not currently recruiting at 196 trial locations

Overseen By Ahmadshah Mirkhel

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Chinook Therapeutics, Inc.

Must be taking: RAS inhibitors

Must not be taking: Immunosuppressants

Disqualifiers: Diabetic kidney disease, Nephrotic syndrome, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 132 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called atrasentan for individuals with IgA nephropathy, a kidney disease that can worsen kidney function. The goal is to determine if atrasentan is safe and effective in slowing the progression of this condition compared to a placebo (a treatment with no active drug). Suitable candidates for this trial include those diagnosed with IgA nephropathy, experiencing significant protein in their urine, and already on stable kidney-related medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you continue taking a stable dose of a RAS inhibitor (a type of blood pressure medication) for at least 12 weeks before joining. If you are on an SGLT2 inhibitor (a diabetes medication), it also needs to be stable for 12 weeks. The protocol does not specify stopping other medications.

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

Research has shown that atrasentan has been tested for safety in patients with IgA nephropathy. In one study, 11.2% of patients taking atrasentan experienced fluid retention, compared to 8.2% of those taking a placebo. This side effect did not lead to discontinuation of treatment. Another review found that using atrasentan with losartan was as safe as using losartan alone, suggesting that atrasentan is generally well-tolerated.

These studies indicate that while some side effects like fluid retention can occur, atrasentan is considered safe. Data from previous patients and clinical reviews support this conclusion. Prospective trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

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

Unlike the standard treatments for IgA Nephropathy, which often include corticosteroids and immunosuppressants to manage symptoms, atrasentan offers a unique approach by targeting the endothelin receptor. This mechanism is exciting because it directly addresses the inflammation and scarring in the kidneys, which are key issues in IgA Nephropathy. Researchers are particularly hopeful about atrasentan because it could provide a more targeted therapy with potentially fewer side effects compared to broader immunosuppressive treatments.

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

Research has shown that atrasentan, which participants in this trial may receive, can significantly reduce protein levels in the urine of patients with IgA nephropathy (IgAN). Specifically, studies found that patients taking atrasentan experienced a noticeable decrease in protein levels compared to those on a placebo. This reduction is crucial because high protein levels in urine are linked to kidney damage. Atrasentan targets pathways that protect the kidneys, potentially slowing the disease's progression. Overall, evidence suggests that atrasentan could be effective for people with IgAN. ^{1 3 4 5 6}

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 IgA Nephropathy, a kidney disease, who have a certain level of kidney function and are on stable doses of specific blood pressure medications. They must not be pregnant or planning to become so during the study. People with high blood pressure, severe anemia, recent cancer (except some skin cancers), other chronic kidney diseases, or those who've had organ transplants can't join.

Inclusion Criteria

You have more than 1 gram of protein in your urine per day, as measured by a 24-hour urine collection test.

Willing and able to provide informed consent and comply with all study requirements

My kidney function test shows an eGFR of 30 or higher.

Exclusion Criteria

I have a significant history of liver problems.

I have had cancer in the last 5 years, but not skin cancer or treated cervical cancer.

I haven't taken any experimental or approved IgAN treatments, except RAS inhibitors, recently.

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 or placebo daily for 132 weeks

132 weeks

Regular visits with options for remote study visits using telemedicine and home health

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with atrasentan 0.75 mg daily for up to 48 weeks

48 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atrasentan
• Placebo

Trial Overview The ALIGN Study is testing Atrasentan against a placebo in patients at risk of worsening kidney function due to IgA Nephropathy. It's a phase 3 trial where participants won't know if they're getting the actual drug or a dummy pill (placebo). The goal is to see if Atrasentan is effective and safe.

How Is the Trial Designed?

Group I: Atrasentan Experimental Treatment 1 Intervention

Double-blind Period: Once daily oral administration of 0.75 mg atrasentan for 132 weeks. Open-label Extension Period: Once daily oral administration of 0.75 mg atrasentan for 48 weeks after completion of 132 weeks on atrasentan or placebo.

Group II: Placebo Placebo Group 1 Intervention

Double-blind Period: Once daily oral administration of placebo for 132 weeks

Who Is Running the Clinical Trial?

Chinook Therapeutics, Inc.

Lead Sponsor

Trials

10

Recruited

1,100+

Chinook Therapeutics U.S., Inc.

Lead Sponsor

Trials

2

Recruited

510+

Published Research Related to This Trial

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]

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]

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. 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 ...

4. 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 ... with primary immunoglobulin A nephropathy ( ...

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05834738

Study Details | NCT05834738 | Randomized, Double-blind, ... The ASSIST study is a phase 2, double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of atrasentan vs. placebo in subjects ...