Abstract: INFO07-FR
The ASSIST Trial: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Atrasentan in Patients with IgA Nephropathy on SGLT2i
Session Information
- Informational Posters - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
- Kotwal, Sradha S., The George Institute for Global Health, Newtown, New South Wales, Australia
- Lim, Soo Kun, Universiti Malaya, Kuala Lumpur, Malaysia
- Noronha, Irene L., Hospital Beneficencia Portuguesa de Sao Paulo, Sao Paulo, Brazil
- 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
- Mottl, Amy K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Description
IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis and has limited treatment options. Endothelin A (ETA) receptor activation drives proteinuria, kidney inflammation and fibrosis. In interim results of a phase 2, open-label study in patients with IgAN (AFFINITY), atrasentan, a potent and selective ETA antagonist, was well tolerated and resulted in clinically meaningful proteinuria reduction. Meanwhile, in a post-hoc analysis in patients with type 2 diabetes and CKD (SONAR), treatment with SGLT2i and atrasentan resulted in greater reductions in albuminuria compared to atrasentan alone (n=14). The ASSIST trial will evaluate the safety and efficacy of atrasentan vs. placebo in adults with IgAN and persistent proteinuria while on stable background of SGLT2i and RASi.
ASSIST (NCT05834738) is a randomized, double-blind, placebo-controlled, crossover study that will enroll ~52 patients with biopsy-proven IgAN and eGFR ≥30 mL/min/1.73 m2 who are receiving max-tolerated RASi for ≥12 wks prior to screening. Patients on a stable dose of SGLT2i prior to screening (SGLT2i stable) must have total urine protein >0.5 g/d at screening. Patients not currently on a stable dose of SGLT2i must have total urine protein >0.85 g/d at screening and enter a run-in period receiving SGLT2i for 8 wks, after which they must have total urine protein >0.5 g/d confirmed at the wk 1 visit. Choice of SGLT2i will be at the discretion of the investigator.
Patients will be randomized 1:1 to receive 0.75 mg atrasentan QD during one period and placebo during the other period. Randomization will be stratified by SGLT2i status (stable vs run-in). Patients will enter Treatment Period 1 for 12 wks, followed by a 12-wk washout, and then Treatment Period 2 for 24 wks. Patients will have follow-up evaluations for safety approximately 4 wks after the end of treatment.
Primary and secondary endpoints are change in UPCR from baseline to wk 12 and wk 24, respectively. Type, incidence, severity, seriousness, and relatedness of AEs will be evaluated. Change in eGFR from baseline to wk 24 in Treatment Period 2 will be evaluated as an exploratory endpoint.
Funding
- Chinook Therapeutics Inc