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 30, 2023
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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 the study may be eligible to enroll in an extension study to receive open-label treatment with atrasentan under a separate protocol.
| 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 |
| Estimated Primary Completion Date : | December 1, 2023 |
| Estimated Study Completion Date : | December 1, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Atrasentan
Once daily oral administration of 0.75 mg atrasentan for 132 weeks
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Drug: Atrasentan
Film-coated tablet
Other Names:
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Placebo Comparator: Placebo
Once daily oral administration of placebo for 132 weeks
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Drug: Placebo
Film-coated tablet |
- Change in proteinuria [ Time Frame: Up to Week 24 or approximately 6 months ]The change in urine protein:creatinine ratio (UPCR) from baseline to Week 24. (non-SGLT2i stratum)
- Change in eGFR [ Time Frame: Up to approximately 2.6 years ]Change from baseline to end of study in eGFR.
- 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/1.73m2, sustained for at least 30 days
- Chronic dialysis ≥30 days
- Kidney transplantation
- All-cause mortality
- 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/1.73m2, sustained for at least 30 days
- Chronic dialysis ≥30 days
- Kidney transplantation
- All-cause mortality
- Change in proteinuria (UPCR) [ Time Frame: Baseline to Week 24 ]1. Change in proteinuria (UPCR) based on 24-hour urine collection in SGLT2i stable stratum compared to Placebo
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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 m2 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.
Exclusion Criteria:
- Current diagnosis with another chronic kidney disease, including diabetic kidney disease.
- History of kidney transplantation or other organ transplantation.
- Use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months.
- Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator.
- Known history of heart failure or a previous hospital admission for fluid overload.
- Clinically significant history of liver disease as assessed by the Investigator.
- Hemoglobin below 9 g/dL as measured by the Investigator or prior history of blood transfusion for anemia within the past 3 months.
- Malignancy within the past 5 years. Exceptions to this criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ.
- For women, pregnancy, breast feeding, or intent to become pregnant during the study. and at least 1 month afterward.
- For men, intent to father a child or donate sperm during the study.
- Have received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor) including SGLT2i (except for subjects in the SGLT2i stable stratum) within 1 month (or 5 half-lives of the agent, whichever is longer) prior to Screening. If the investigational agent is a cytotoxic or immunosuppressive agent then this washout period is 6 months.
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: | Charlotte Jones-Burton, MD, MS | SVP, Product Development & Strategy |
| 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 30, 2023 |
| Last Verified: | May 2023 |
| 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 |