Abstract: INFO27
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atrasentan in Patients With IgA Nephropathy: The ALIGN 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
- L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
- Jardine, Meg, University of Sydney, Sydney, New South Wales, Australia
- Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Levin, Adeera, The 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
- Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
- Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
- Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, United States
- King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
- Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
Description
IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis. Up to 40% of patients with IgAN are at risk of progressing to ESKD and proteinuria is the strongest predictor of disease progression. Endothelin A (ETA) receptor activation drives proteinuria, kidney inflammation, and fibrosis. Therefore, atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. Atrasentan has 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 atrasentan AFFINITY study have shown a reduction in proteinuria at week 12 in 18 patients with a generally well tolerated safety profile.
The ongoing ALIGN study (NCT04573478) is a global, phase 3, randomized, double-blind, placebo-controlled study to determine the effect of atrasentan in patients with IgAN who are at high risk of kidney function loss. Approximately 320 patients will be enrolled across North America, South America, Europe, and Asia-Pacific with biopsy-proven IgAN with total protein excretion ≥ 1 g per 24 hr and eGFR ≥30 mL/min/1.73 m2. Patients will continue to receive a maximally tolerated and stable dose of a RASi; a limited number of patients (up to 5%) that are unable to tolerate RASi therapy may be enrolled. An additional stratum of up to 64 patients receiving a stable dose of SGLT2i for at least 12 weeks will be enrolled.
Patients will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Options for remote study visits using telemedicine and home health visits are available. The primary outcome is change in proteinuria at Week 24. Secondary measures include change from baseline in eGFR, safety, and tolerability, and quality of life.
Funding
- Chinook Therapeutics
Abstract: INFO27
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, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category:
- No subcategory defined
Authors
- L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
- Jardine, Meg, University of Sydney, Sydney, New South Wales, Australia
- Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Levin, Adeera, The 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
- Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
- Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
- Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, United States
- King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
- Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
Description
IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis. Up to 40% of patients with IgAN are at risk of progressing to ESKD and proteinuria is the strongest predictor of disease progression. Endothelin A (ETA) receptor activation drives proteinuria, kidney inflammation, and fibrosis. Therefore, atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. Atrasentan has 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 atrasentan AFFINITY study have shown a reduction in proteinuria at week 12 in 18 patients with a generally well tolerated safety profile.
The ongoing ALIGN study (NCT04573478) is a global, phase 3, randomized, double-blind, placebo-controlled study to determine the effect of atrasentan in patients with IgAN who are at high risk of kidney function loss. Approximately 320 patients will be enrolled across North America, South America, Europe, and Asia-Pacific with biopsy-proven IgAN with total protein excretion ≥ 1 g per 24 hr and eGFR ≥30 mL/min/1.73 m2. Patients will continue to receive a maximally tolerated and stable dose of a RASi; a limited number of patients (up to 5%) that are unable to tolerate RASi therapy may be enrolled. An additional stratum of up to 64 patients receiving a stable dose of SGLT2i for at least 12 weeks will be enrolled.
Patients will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Options for remote study visits using telemedicine and home health visits are available. The primary outcome is change in proteinuria at Week 24. Secondary measures include change from baseline in eGFR, safety, and tolerability, and quality of life.
Abstract: INFO27
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atrasentan in Patients With IgA Nephropathy: The ALIGN 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
- L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
- Jardine, Meg, University of Sydney, Sydney, New South Wales, Australia
- Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Levin, Adeera, The 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
- Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
- Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
- Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, United States
- King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
- Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
Description
IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis. Up to 40% of patients with IgAN are at risk of progressing to ESKD and proteinuria is the strongest predictor of disease progression. Endothelin A (ETA) receptor activation drives proteinuria, kidney inflammation, and fibrosis. Therefore, atrasentan, a potent and selective ETA antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. Atrasentan has 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 atrasentan AFFINITY study have shown a reduction in proteinuria at week 12 in 18 patients with a generally well tolerated safety profile.
The ongoing ALIGN study (NCT04573478) is a global, phase 3, randomized, double-blind, placebo-controlled study to determine the effect of atrasentan in patients with IgAN who are at high risk of kidney function loss. Approximately 320 patients will be enrolled across North America, South America, Europe, and Asia-Pacific with biopsy-proven IgAN with total protein excretion ≥ 1 g per 24 hr and eGFR ≥30 mL/min/1.73 m2. Patients will continue to receive a maximally tolerated and stable dose of a RASi; a limited number of patients (up to 5%) that are unable to tolerate RASi therapy may be enrolled. An additional stratum of up to 64 patients receiving a stable dose of SGLT2i for at least 12 weeks will be enrolled.
Patients will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Options for remote study visits using telemedicine and home health visits are available. The primary outcome is change in proteinuria at Week 24. Secondary measures include change from baseline in eGFR, safety, and tolerability, and quality of life.