Atrasentan in Patients With IgA Nephropathy
- Conditions
- IgA NephropathyImmunoglobulin A Nephropathy
- Interventions
- Drug: Placebo
- Registration Number
- NCT04573478
- Lead Sponsor
- Chinook Therapeutics, Inc.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 404
Double-Blind period:
- Biopsy-proven IgA nephropathy.
- Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks. Exceptions from this requirement will be made for subjects who are unable to tolerate RAS inhibitor therapy.
- Total urine protein ≥1 g/day as measured via 24-hour urine collection by central laboratory at Screening.
- eGFR of at least 30 mL/min/1.73 m^2 at Screening based on the CKD-EPI equation.
- Willing and able to provide informed consent and comply with all study requirements.
- SGLT2i Stable Stratum Only - Receiving a stable dose of an SGLT2i (per Investigator choice) in addition to a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to Screening.
- All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been started at least 1 month prior to Baseline.
Open-Label Period:
- Willing and able to provide informed consent and comply with all OL extension study visits and study procedures.
- Completed treatment through Week 132 and completed the Week 136 visit.
- All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been continued after completing the double-blind portion of the study.
Double-blind period:
- Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy.
- Clinical diagnosis of nephrotic syndrome.
- BNP value of > 200 pg/mL at Screening.
- Platelet count <80,000 per μL at Screening.
- History of organ transplantation (subjects with history of corneal transplant are not excluded).
- Use of systemic immunosuppressant medications.
- Hemoglobin below 9 g/dL at Screening or prior history of blood transfusion for anemia within 3 months of Screening.
Open-label period:
- eGFR < 25 mL/min/1.73m^2 or evidence of rapidly decreasing eGFR, including unrecovered acute kidney injury or expected to require renal replacement therapy within 3 months
- BNP value of > 200 pg/mL at OL Screening.
- Platelet count < 80,000 per μL at OL Screening.
- Hemoglobin below 9 g/dL at OL screening or prior history of blood transfusion for anemia within 3 months of OL Screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Double-blind Period: Once daily oral administration of placebo for 132 weeks Atrasentan Atrasentan Double-blind Period: Once daily oral administration of 0.75 mg atrasentan for 132 weeks. Open-label Extension Period: Once daily oral administration of 0.75 mg atrasentan for 48 weeks after completion of 132 weeks on atrasentan or placebo.
- Primary Outcome Measures
Name Time Method Double-blind period: Change in proteinuria Up to Week 36 or approximately 9 months The change in urine protein:creatinine ratio (UPCR) from baseline to Week 36. (non-SGLT2i stratum)
Open-label period: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) From open-label baseline up to end of treatment visit, 48 weeks Type, incidence, severity, seriousness, and relatedness of TEAEs.
Open-label period: Number of Subjects With Adverse Events of Special Interest (AESI) Including Events of Fluid Overload From open-label baseline up to end of treatment visit, 48 weeks Incidence, severity, seriousness, and relatedness AESIs.
- Secondary Outcome Measures
Name Time Method Double-blind period: Change in eGFR Up to Week 136, 4 weeks post end of treatment 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)
Open-label period: Change in proteinuria Open-label Baseline to open-label Week 36 Change in UPCR based on 24-hour urine collection.
Open-label period: Change in eGFR Open-label Baseline to open-label Week 52 Change from open-label Baseline to open-label Week 52 using the CKD-EPI creatinine equation.
Double-blind period: Percent of subjects meeting the first composite endpoint Up to approximately 2.6 years 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 mortalityDouble-blind period: Percent of subjects meeting the second composite endpoint Up to approximately 2.6 years 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 mortalityDouble-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36 Baseline to 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).
Double-blind period: Number of Subjects With TEAEs From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks Type, incidence, severity, seriousness, and relatedness of TEAEs.
Double-blind period: Number of Subjects With AESI Including Events of Fluid Overload From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks Incidence, severity, seriousness, and relatedness AESIs.
Related Research Topics
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Trial Locations
- Locations (134)
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
🇺🇸Fort Wayne, Indiana, United States
University of Louisville Physicians- Kidney Disease Program
🇺🇸Louisville, Kentucky, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Intermed Consultants
🇺🇸Minneapolis, Minnesota, United States
Scroll for more (124 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States