Atrasentan for IgA Nephropathy

(ASSIST Trial)

Not currently recruiting at 29 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

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 safety and effectiveness for people with IgA nephropathy, a kidney disease that affects waste filtration. Participants will take either atrasentan or a placebo (a pill with no active drug) at different stages to compare results. Eligible participants must have a diagnosis of IgA nephropathy and be taking specific kidney medications, including an SGLT2 inhibitor. As a Phase 2 trial, this research focuses on measuring 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're 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 generally safe for people with IgA nephropathy (IgAN). In one study, patients who took atrasentan alongside their regular treatment experienced a steady and significant decrease in protein in their urine over a year. This finding suggests that the treatment might help protect kidney function without causing major side effects.

Other studies have also confirmed the safety of atrasentan. They found that patients tolerated it well, with no serious side effects reported. While some side effects might occur, they are usually not severe. Overall, past research supports the safety of atrasentan for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for IgA nephropathy focus on controlling symptoms and slowing progression using medications like corticosteroids or immunosuppressants. But atrasentan works differently, targeting the endothelin pathway, which is involved in kidney damage. Researchers are excited about atrasentan because it offers a novel approach by potentially reducing proteinuria, a key marker of kidney disease, without the side effects often associated with current treatments. This new mechanism could mean improved outcomes for patients with fewer complications.

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

Research has shown that atrasentan may be very helpful in treating IgA nephropathy (IgAN). Studies have demonstrated that atrasentan significantly reduces proteinuria, meaning fewer excess proteins in the urine—a major issue in IgAN. One study found a 36% drop in proteinuria after 36 weeks of treatment. These positive results lasted for over a year, indicating the treatment's long-term benefits. Atrasentan was also well-tolerated when used with standard treatments. In this trial, participants will receive atrasentan in one of the treatment sequences, suggesting that atrasentan could be an effective option for managing IgAN. ^{2 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 people with IgA Nephropathy, a kidney disease. Participants must be on standard care and an SGLT2 inhibitor. Specific inclusion and exclusion criteria details are not provided but typically include factors like age, disease severity, and other health conditions.

Inclusion Criteria

eGFR of at least 30 mL/min/1.73 m^2 at screening based on the 2021 CKD-EPI equation.

My kidney disease was confirmed by a biopsy to be IgA nephropathy.

Willing to agree to highly effective forms of contraception, as specified in the protocol, throughout the study and for up to 1 month afterward. In WOCBP, use of hormonal contraceptive agents must have been started at least 1 month prior to baseline.

Exclusion Criteria

I have a chronic kidney condition besides my current diagnosis.

Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator.

Known history of heart failure or prior hospital admissions for conditions relating to fluid overload that in the opinion of the Principal Investigator or Sponsor might confound the results of the study or pose additional risk to the participant by their participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

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

8 weeks

Treatment Period A

Participants receive 0.75 mg atrasentan once daily for 12 weeks

12 weeks

Pre-dose visits on 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

Pre-dose visits on 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

Trial Overview The ASSIST study tests the safety and effectiveness of Atrasentan compared to a placebo in patients with IgA Nephropathy. It's a phase 2 trial where participants receive both treatments at different times without knowing which one they're getting (double-blind).

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?

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

Recent randomized controlled trial results suggest that comprehensive supportive care is more beneficial than immunosuppressive therapy for patients with IgA nephropathy who are at high risk for disease progression.

The findings highlight the ongoing debate regarding the role of immunosuppressive therapy in treating IgA nephropathy, indicating a shift towards supportive care as a preferred approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppression in IgA nephropathy: how certain are we? Floege, J., Rauen, T.[2017]

IgA nephropathy (IgAN) can lead to serious kidney disease, with 25-30% of patients progressing to end-stage renal disease within 20 years, highlighting the need for effective treatments.

Current management strategies for IgAN are limited, with no consensus on immunosuppressive therapy, and patients at high risk for progression should be treated aggressively for hypertension and proteinuria to protect kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of IgA nephropathy. Barratt, J., Feehally, J.[2006]

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]

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]

Combining valsartan with clopidogrel and leflunomide significantly reduced proteinuria in patients with progressive IgA nephropathy, with reductions of 62.35% and 69.47% in the respective treatment groups after 24 months.

The combination treatment was associated with minimal adverse reactions and improved renal function compared to valsartan alone, suggesting it could be a safer and more effective option for managing IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. Cheng, G., Liu, D., Margetts, P., et al.[2018]

Citations

1. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2409415

Atrasentan in Patients with IgA Nephropathy In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924023830

1-year results of atrasentan in IgA nephropathy (IgAN) Atrasentan, in addition to standard of care, was well tolerated and resulted in a clinically meaningful, stable reduction in proteinuria over 1 year of ...

3. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/affinity_study__1_year_results_of_atrasentan_in.2378.aspx

AFFINITY Study: 1-Year Results of Atrasentan in IgA... Conclusion: Atrasentan, in addition to standard of care, was well tolerated and resulted in a clinically meaningful, stable reduction in proteinuria over 1 year ...

4. checkrare.com checkrare.com/efficacy-of-atrasentan-to-treat-patients-with-iga-nephropathy/

Efficacy of Atrasentan To Treat Patients With IgA ... Based on data from the interim analysis, atrasentan has achieved statistically significant reductions of 36% in proteinuria at week 36 compared ...

5. 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 ...

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) ...