Abstract: INFO36
Atrasentan in Patients With Proteinuric Glomerular Diseases: The AFFINITY 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
- Rastogi, Anjay, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
- Wong, Muh Geot, Royal North Shore Hospital, St Leonards, New South Wales, Australia
- Camargo, Marianne, Chinook therapeutics, Inc, Seattle, Washington, United States
- King, Andrew J., Chinook therapeutics, Inc, Seattle, Washington, United States
- Lewis, Sandy, Chinook therapeutics, Inc, Seattle, Washington, United States
- Tolentino, Jerlyn C., Chinook therapeutics, Inc, Seattle, Washington, United States
- Glicklich, Alan, Chinook therapeutics, Inc, Seattle, Washington, United States
- Packham, David K., Melbourne Renal Research Group, Reservoir, Victoria, Australia
Description
Background: Glomerular diseases are the leading cause of end stage kidney disease (ESKD) worldwide. Immunoglobulin A nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), Alport syndrome, and diabetic kidney disease (DKD) are all characterized by proteinuria, which is a strong predictor of disease progression and ESKD. Endothelin A (ETA) receptor activation drives proteinuria, along with kidney inflammation and fibrosis. Atrasentan, a potent and selective ETA antagonist, targets a key pathogenic pathway common to the progression of proteinuric glomerular disease of different underlying etiologies. Atrasentan has been studied in over 5,300 patients with DKD, showing clinically significant and sustained reductions in proteinuria when administered on top of a maximum tolerated dose of RAS inhibitor (RASi).
Objective: A global, phase 2, open-label basket study is underway to study efficacy and safety of atrasentan in IgAN, FSGS, Alport syndrome and DKD patients at risk of progressive loss of kidney function.
Methods: Approximately 80 patients in the United States, Australia, South Korea, Spain, Italy, and the United Kingdom with proteinuric glomerular diseases will be enrolled in a basket study to receive 0.75 mg atrasentan orally for 52 weeks. Four cohorts are planned, each consisting of 20 patients with the following diseases: IgAN, Alport syndrome, FSGS, and DKD. Patients must be receiving a maximally tolerated and stable dose of RASi and patients with DKD must also be on a stable dose of a SGLT2i. Proteinuria must be present in all patients: IgAN (urine protein creatinine ratio (UPCR) between 0.5 and < 1.0 g/g), FSGS (UPCR > 1.5 g/g), Alport syndrome (UPCR > 0.5 g/g), and DKD [urine albumin creatinine ration (UACR) ≥ 0.5 g/g]. Patients must also have an eGFR ≥ 30 mL/min/1.73 m2 (≥ 45 mL/min/1.73 m2 for the DKD patients). Participants will have study assessments over 1 year with options for remote study visits using telemedicine and home health visits. The primary objective is to evaluate the effect of atrasentan on change in proteinuria (IgAN, FSGS, AS) or albuminuria (DKD) from baseline at Week 12. Key exploratory objectives include changes in eGFR from Baseline to Week 52 and changes in audiology assessments in patients with Alport syndrome.
Funding
- Chinook Therapeutics, Inc