Atrasentan in Patients With IgA Nephropathy (ALIGN)
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| ClinicalTrials.gov Identifier: NCT04573478 |
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Recruitment Status :
Active, not recruiting
First Posted : October 5, 2020
Last Update Posted : May 3, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| IgA Nephropathy Immunoglobulin A Nephropathy | Drug: Atrasentan Drug: Placebo | Phase 3 |
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 (Clinical Trial) |
| Estimated Enrollment : | 380 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Masking Description: | Double-blind |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Atrasentan in Patients With IgA Nephropathy at Risk of Progressive Loss of Renal Function |
| Actual Study Start Date : | December 11, 2020 |
| Actual Primary Completion Date : | September 7, 2023 |
| Estimated Study Completion Date : | December 1, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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. |
Drug: Atrasentan
Film-coated tablet
Other Names:
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Placebo Comparator: Placebo
Double-blind Period: Once daily oral administration of placebo for 132 weeks
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Drug: Placebo
Film-coated tablet |
- Double-blind period: Change in proteinuria [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: From open-label baseline up to end of treatment visit, 48 weeks ]Incidence, severity, seriousness, and relatedness AESIs.
- Double-blind period: Change in eGFR [ Time Frame: 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)
- Double-blind period: Percent of subjects meeting the first composite endpoint [ Time Frame: 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 mortality
- Double-blind period: Percent of subjects meeting the second composite endpoint [ Time Frame: 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 mortality
- Double-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
- Open-label period: Change in proteinuria [ Time Frame: Open-label Baseline to open-label Week 36 ]Change in UPCR based on 24-hour urine collection.
- Open-label period: Change in eGFR [ Time Frame: Open-label Baseline to open-label Week 52 ]Change from open-label Baseline to open-label Week 52 using the CKD-EPI creatinine equation.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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.
Exclusion Criteria:
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04573478
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| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Chinook Therapeutics U.S., Inc. |
| ClinicalTrials.gov Identifier: | NCT04573478 |
| Other Study ID Numbers: |
CHK01-01 |
| First Posted: | October 5, 2020 Key Record Dates |
| Last Update Posted: | May 3, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Kidney Diseases Kidney Disease, Chronic Urologic Diseases Glomerulonephritis |
Glomerular Disease Glomerulonephritis, IGA Glomerulopathy Immunoglobulin Disease |
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Kidney Diseases Glomerulonephritis, IGA Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases Glomerulonephritis |
Nephritis Autoimmune Diseases Immune System Diseases Atrasentan Antineoplastic Agents Endothelin A Receptor Antagonists Endothelin Receptor Antagonists Molecular Mechanisms of Pharmacological Action |