Abstract: INFO15-TH
The AFFINITY Trial: An Open-Label Phase 2 Study of Atrasentan in Patients with Proteinuric Glomerular Diseases
Session Information
- Informational Posters - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
- Pedagogos, Eugenia, Western Health, Sunshine, Victoria, Australia
- Rheault, Michelle N., University of Minnesota, Minneapolis, Minnesota, United States
- Rizk, Dana V., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Beckett, Valeria, Chinook Therapeutics, Seattle, Washington, United States
- Brahmbhatt, Yasmin G., Chinook Therapeutics, Seattle, Washington, United States
- Camargo, Marianne, Chinook Therapeutics, Seattle, Washington, United States
- Jones-Burton, Charlotte, Chinook Therapeutics, Seattle, Washington, United States
- King, Andrew J., Chinook Therapeutics, Seattle, Washington, United States
- Udani, Suneel M., Nephrology Associates of Northern Illinois and Indiana, Hinsdale, Illinois, United States
Description
Glomerular diseases are the leading cause of ESKD worldwide. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), Alport syndrome (AS) and diabetic kidney disease (DKD) are important glomerular diseases characterized by proteinuria, a predictor of disease progression and ESKD. Endothelin A (ETA) receptor activation drives proteinuria, inflammation and fibrosis. Atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in glomerular diseases. Atrasentan has previously demonstrated clinically meaningful and sustained proteinuria reduction with an acceptable safety profile in patients with DKD and in interim results from the IgAN cohort of the ongoing AFFINITY trial.
The AFFINITY trial (NCT04573920) is an ongoing, global, phase 2, open-label basket study evaluating the safety and efficacy of atrasentan in patients with IgAN, AS, DKD and two FSGS dose cohorts enrolling approximately 20 patients per cohort. Proteinuria must be present in all patients: IgAN, UPCR ≥ 0.5 and < 1.0 g/g; FSGS, UPCR > 1.0 g/g; AS, UPCR > 0.5 g/g; DKD, UACR ≥ 0.5 g/g. Patients with IgAN, AS or FSGS must also have an eGFR ≥ 30 mL/min/1.73 m2 and patients with DKD must have eGFR ≥ 45 mL/min/1.73 m2. Patients must be receiving a maximally tolerated RASi and patients with DKD must also be on SGLT2i.
Patients with IgAN, AS and DKD receive 0.75 mg oral atrasentan daily for 52 weeks. One FSGS cohort will receive 0.75 mg daily for at least 12 weeks with optional dose escalation to 1.5 mg daily through the remainder of the study period. These four cohorts have completed enrollment. Enrollment is ongoing for an additional FSGS cohort which will receive 0.75 mg daily for 6 weeks followed by 1.5 mg daily if tolerated for the remainder of the study period.
The primary endpoint is change in UPCR (IgAN, FSGS, AS) or UACR (DKD) from baseline at Week 12 for IgAN, AS and DKD, and at week 24 post dose escalation for FSGS. Key exploratory measures include change in eGFR from baseline to Week 52. Patients are eligible to continue in a treatment extension period for up to 84 weeks.
Funding
- Chinook Therapeutics