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To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

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Abstract: INFO31

Atrasentan in Patients With Proteinuric Glomerular Diseases: The AFFINITY Study

Session Information

  • Informational Posters
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • Rheault, Michelle N., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Akinfolarin, Akinwande A., Dallas Nephrology Associates, Dallas, Texas, United States
  • Han, Seung Hyeok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • DeVries, Todd, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
  • King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, 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. Therefore, atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in glomerular diseases. Atrasentan has previously demonstrated clinically significant and sustained proteinuria reduction with an acceptable safety profile in over 5,300 patients with DKD. Interim results from the IgAN cohort of the ongoing AFFINITY study have shown a reduction in proteinuria at week 12 in 18 patients with a generally well-tolerated safety profile.

The AFFINITY study (NCT04573920) is an ongoing, global, phase 2, open-label basket study of safety and efficacy of atrasentan in IgAN, FSGS, AS and DKD patients at risk of progressive loss of kidney function. Approximately 100 patients in the United States, Australia, South Korea, Spain, Italy, and United Kingdom will be enrolled. Proteinuria must be present in all patients: IgAN, urine protein creatinine ratio (UPCR) ≥ 0.5 and < 1.0 g/g; FSGS, UPCR > 1.0 g/g; AS, UPCR > 0.5 g/g; DKD, urine albumin creatinine ration (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.

Up to twenty patients per cohort with IgAN, AS and DKD will receive 0.75 mg atrasentan orally QD for 52 weeks. Two twenty-patient FSGS cohorts will be enrolled: one FSGS cohort will receive 0.75 mg for at least 12 weeks with optional dose escalation to 1.5 mg; the second FSGS cohort will receive 0.75 mg for 6 weeks followed by 1.5 mg for the remainder of the study period. The primary outcome is change in proteinuria (IgAN, FSGS, AS) or albuminuria (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.

Funding

  • Chinook Therapeutics
Abstract: INFO31

Atrasentan in Patients With Proteinuric Glomerular Diseases: The AFFINITY Study

Session Information

  • Informational Posters
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Rheault, Michelle N., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Akinfolarin, Akinwande A., Dallas Nephrology Associates, Dallas, Texas, United States
  • Han, Seung Hyeok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • DeVries, Todd, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
  • King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, 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. Therefore, atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in glomerular diseases. Atrasentan has previously demonstrated clinically significant and sustained proteinuria reduction with an acceptable safety profile in over 5,300 patients with DKD. Interim results from the IgAN cohort of the ongoing AFFINITY study have shown a reduction in proteinuria at week 12 in 18 patients with a generally well-tolerated safety profile.

The AFFINITY study (NCT04573920) is an ongoing, global, phase 2, open-label basket study of safety and efficacy of atrasentan in IgAN, FSGS, AS and DKD patients at risk of progressive loss of kidney function. Approximately 100 patients in the United States, Australia, South Korea, Spain, Italy, and United Kingdom will be enrolled. Proteinuria must be present in all patients: IgAN, urine protein creatinine ratio (UPCR) ≥ 0.5 and < 1.0 g/g; FSGS, UPCR > 1.0 g/g; AS, UPCR > 0.5 g/g; DKD, urine albumin creatinine ration (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.

Up to twenty patients per cohort with IgAN, AS and DKD will receive 0.75 mg atrasentan orally QD for 52 weeks. Two twenty-patient FSGS cohorts will be enrolled: one FSGS cohort will receive 0.75 mg for at least 12 weeks with optional dose escalation to 1.5 mg; the second FSGS cohort will receive 0.75 mg for 6 weeks followed by 1.5 mg for the remainder of the study period. The primary outcome is change in proteinuria (IgAN, FSGS, AS) or albuminuria (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.

Abstract: INFO31

Atrasentan in Patients With Proteinuric Glomerular Diseases: The AFFINITY Study

Session Information

  • Informational Posters
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Rheault, Michelle N., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Akinfolarin, Akinwande A., Dallas Nephrology Associates, Dallas, Texas, United States
  • Han, Seung Hyeok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • DeVries, Todd, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
  • King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, 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. Therefore, atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in glomerular diseases. Atrasentan has previously demonstrated clinically significant and sustained proteinuria reduction with an acceptable safety profile in over 5,300 patients with DKD. Interim results from the IgAN cohort of the ongoing AFFINITY study have shown a reduction in proteinuria at week 12 in 18 patients with a generally well-tolerated safety profile.

The AFFINITY study (NCT04573920) is an ongoing, global, phase 2, open-label basket study of safety and efficacy of atrasentan in IgAN, FSGS, AS and DKD patients at risk of progressive loss of kidney function. Approximately 100 patients in the United States, Australia, South Korea, Spain, Italy, and United Kingdom will be enrolled. Proteinuria must be present in all patients: IgAN, urine protein creatinine ratio (UPCR) ≥ 0.5 and < 1.0 g/g; FSGS, UPCR > 1.0 g/g; AS, UPCR > 0.5 g/g; DKD, urine albumin creatinine ration (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.

Up to twenty patients per cohort with IgAN, AS and DKD will receive 0.75 mg atrasentan orally QD for 52 weeks. Two twenty-patient FSGS cohorts will be enrolled: one FSGS cohort will receive 0.75 mg for at least 12 weeks with optional dose escalation to 1.5 mg; the second FSGS cohort will receive 0.75 mg for 6 weeks followed by 1.5 mg for the remainder of the study period. The primary outcome is change in proteinuria (IgAN, FSGS, AS) or albuminuria (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.