The ALIGN Study is a phase 3, double-blind, placebo-controlled study to compare the efficacy and safety of atrasentan to placebo in patients with IgA nephropathy (IgAN) at risk of progressive loss of renal function.
Approximately 320 patients with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Subjects receive a maximally tolerated and stable dose of a RAS (renin-angiotensin system) inhibitor \[such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)\] as part of standard of care. An exception will be made for subjects who are unable to tolerate RAS inhibitor therapy. Additional subjects receiving a stable dose of SGLT2i will be enrolled to the study. Enrollment in this SGLT2i stable stratum will be in accordance with local regulations in regions that prescribe SGLT2i and will be independent of the 320 subjects enrolled for the primary and secondary analyses. The primary objective of the study is to evaluate the effect of atrasentan versus placebo on proteinuria as measured by UPCR. Secondary and tertiary objectives include evaluating the change in kidney function over time as measured by eGFR, safety and tolerability, as well as quality of life. Subjects will have assessments of safety and efficacy over 2 ½ years. To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered. Subjects who complete treatment through Week 132 and complete the double-blinded portion of the study may be eligible to enroll in the open label extension of the study to receive atrasentan 0.75 mg daily for up to 48 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
404
Film-coated tablet
Film-coated tablet
Double-blind period: Change in proteinuria
The change in urine protein:creatinine ratio (UPCR) from baseline to Week 36. (non-SGLT2i stratum)
Time frame: Up to Week 36 or approximately 9 months
Open-label period: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
Type, incidence, severity, seriousness, and relatedness of TEAEs.
Time frame: From open-label baseline up to end of treatment visit, 48 weeks
Open-label period: Number of Subjects With Adverse Events of Special Interest (AESI) Including Events of Fluid Overload
Incidence, severity, seriousness, and relatedness AESIs.
Time frame: From open-label baseline up to end of treatment visit, 48 weeks
Double-blind period: Change in eGFR
Change from Baseline to final study visit (Week 136, 4 weeks post end of treatment) using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation (non-SGLT2i stratum)
Time frame: Up to Week 136, 4 weeks post end of treatment
Double-blind period: Percent of subjects meeting the first composite endpoint
Percent of subjects in the non-SGLT2i stratum meeting the composite endpoint of experiencing at least one of the following during the study: * At least a 30% reduction in eGFR sustained for at least 30 days * eGFR \<15 mL/min/1.73m\^2, sustained for at least 30 days * Chronic dialysis ≥30 days * Kidney transplantation * All-cause mortality
Time frame: Up to approximately 2.6 years
Double-blind period: Percent of subjects meeting the second composite endpoint
Percent of subjects in the non-SGLT2i stratum meeting the composite endpoint of experiencing at least one of the following during the study: * At least a 40% reduction in eGFR sustained for at least 30 days * eGFR \<15 mL/min/1.73m\^2, sustained for at least 30 days * Chronic dialysis ≥30 days * Kidney transplantation * All-cause mortality
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Comprehensive Research Institute
Alhambra, California, United States
Kidney Disease Medical Group
Glendale, California, United States
Stanford University
Stanford, California, United States
University of Florida
Gainesville, Florida, United States
GA Nephrology Associates
Lawrenceville, Georgia, United States
NANI Research, LLC
Hinsdale, Illinois, United States
NANI Research, LLC
Fort Wayne, Indiana, United States
University of Louisville Physicians- Kidney Disease Program
Louisville, Kentucky, United States
Tufts Medical Center
Boston, Massachusetts, United States
...and 125 more locations
Time frame: Up to approximately 2.6 years
Double-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36
Percentage of subjects with reduction of proteinuria to \< 1 g/day and a 25% decrease in total urine protein from Baseline (non-SGLT2i stratum).
Time frame: Baseline to Week 36
Double-blind period: Number of Subjects With TEAEs
Type, incidence, severity, seriousness, and relatedness of TEAEs.
Time frame: From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
Double-blind period: Number of Subjects With AESI Including Events of Fluid Overload
Incidence, severity, seriousness, and relatedness AESIs.
Time frame: From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
Open-label period: Change in proteinuria
Change in UPCR based on 24-hour urine collection.
Time frame: Open-label Baseline to open-label Week 36
Open-label period: Change in eGFR
Change from open-label Baseline to open-label Week 52 using the CKD-EPI creatinine equation.
Time frame: Open-label Baseline to open-label Week 52