Abstract: INFO35
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atrasentan in Patients With IgA Nephropathy: The ALIGN Study
Session Information
- Informational Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
- Jardine, Meg, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia
- Kohan, Donald E., The University of Utah School of Medicine, Salt Lake City, Utah, United States
- Lafayette, Richard A., Stanford University School of Medicine, Stanford, California, United States
- Levin, Adeera, University of British Columbia, Vancouver, British Columbia, Canada
- Liew, Adrian, Mount Elizabeth Novena Hospital, Singapore, Singapore
- Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China
- Glicklich, Alan, Chinook Therapeutics, Seattle, Washington, United States
- Camargo, Marianne, Chinook Therapeutics, Seattle, Washington, United States
- King, Andrew J., Chinook Therapeutics, Seattle, Washington, United States
- Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
Description
Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Up to 40% of patients with IgAN are at risk of progressing to end-stage kidney disease (ESKD), proteinuria is the strongest predictor of progression. 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 >5,000 patients in a global phase 3 outcome clinical trial in patients with diabetic kidney disease who were on a maximum tolerated dose of RAS inhibitor (RASi). Results showed a 35% reduced risk of the primary composite outcome of doubling of serum creatinine or ESKD (95% CI: 0.49, 0.88; P = 0.005). The most common adverse event was fluid retention.
Selective ETA blockade represents a promising approach to reduce proteinuria and preserve kidney function in patients with IgAN at high risk of progression.
Objective:
A global, phase 3, double-blind, placebo-controlled study is in progress to determine the effect of atrasentan in patients with IgAN who are at high risk of kidney function loss.
Methods:
Approximately 320 patients 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 continue receiving a maximally tolerated and stable dose of a RASi as standard of care. The study will also include patients that are unable to tolerate RASi 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 two and a half years with options for remote study visits using telemedicine and home health visits. The primary objective is to evaluate change in proteinuria at Week 24. Secondary objectives include change from baseline in eGFR, safety, and tolerability, and quality of life.
Funding
- Chinook Therapeutics