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Kidney Week

Abstract: INFO29

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atrasentan in Patients with IgA Nephropathy (The ALIGN Study)

Session Information

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States
  • Lafayette, Richard A., Stanford Medicine, Stanford, California, United States
  • Levin, Adeera, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  • Perkovic, Vlado, University of New South Wales Faculty of Medicine, Sydney, New South Wales, Australia
  • Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China
  • King, Andrew J., Chinook Therapeutics, Seattle, Washington, United States
  • Glicklich, Alan, Chinook Therapeutics, Seattle, Washington, United States
  • Barratt, Jonathan, University of Leicester Medical School, Leicester, Leicester, United Kingdom
Description

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally and an important cause of chronic kidney disease (CKD). Up to 40% of IgAN patients are at risk of progressing to end-stage kidney disease (ESKD) and proteinuria is the strongest predictor of progression. There are no approved therapies for IgAN, leaving an important need for new strategies to lower proteinuria and preserve kidney function in high risk patients.
Endothelin A (ETA) receptor activation drives proteinuria, along with kidney inflammation and fibrosis. Atrasentan, a potent and selective ETA antagonist, has been studied extensively in >5,300 patients with type 2 diabetes and kidney disease (DKD), demonstrating clinically significant and sustained reductions in proteinuria when administered on top of a maximum tolerated dose of RAS inhibitor (RASi). In a global Phase 3 outcome study in DKD (SONAR), atrasentan lowered albuminuria and reduced the risk of major kidney events. The most common adverse event was fluid retention.
Selective ETA blockade represents a potential approach to reduce proteinuria and preserve kidney function in high risk IgAN patients.
Objective: A global, phase 3, double-blind, placebo-controlled study is planned to determine the effect of atrasentan in IgAN patients at high risk of kidney function loss.
Methods: Approximately 320 partients across North America, South America, Europe, and Asia-Pacific with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Patients will be receiving a maximally tolerated and stable dose of RAS inhibitor. The study will include a cohort of patients that are unable to tolerate RAS inhibitor therapy. Additional eligibility criteria include urine protein creatinine ratio (UPCR) ≥1 g/g and eGFR ≥30 mL/min/1.73 m2. Participants will have study assessments over 2 ½ years with options for remote study visits using telemedicine and home health. The primary objective is to evaluate the effect of atrasentan versus placebo on UPCR. Secondary objectives include evaluating the change in eGFR over time, safety and tolerability, as well as quality of life.

Funding

  • Chinook Therapeutics