Atrasentan in Patients With IgA Nephropathy (ALIGN)

• ClinicalTrials.gov Identifier: NCT04573478
• Recruitment Status: Active, not recruiting
• First Posted: October 5, 2020
• Last Update Posted: May 3, 2024
• Sponsor: Chinook Therapeutics U.S., Inc.
• Information provided by (Responsible Party): Chinook Therapeutics, Inc. ( Chinook Therapeutics U.S., Inc. )

Tracking Information

• First Submitted Date: September 12, 2020
• First Posted Date: October 5, 2020
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: December 11, 2020
• Actual Primary Completion Date: September 7, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2024)

• 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.

Original Primary Outcome Measures (submitted: September 28, 2020)

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

Current Secondary Outcome Measures (submitted: May 2, 2024)

• 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.

Original Secondary Outcome Measures (submitted: September 28, 2020)

• Change in eGFR [ Time Frame: Up to week 136 or approximately 2.6 years ]
  Change from baseline to end of study in eGFR
• Rate of change in eGFR [ Time Frame: Up to week 120 or approximately 2.3 years ]
  Rate of change in eGFR during 2 years on treatment at Week 12 through to Week 120
• Rate of change in eGFR [ Time Frame: Up to week 136 or approximately 2.6 years ]
  Rate of change in eGFR during the study from baseline to Week 136
• Percent of subjects with specified proteinuria/UPCR change [ Time Frame: Up to week 136 or approximately 2.6 years ]
  Percent of subjects achieving proteinuria < 1 g/day at Week 24 and 40% reduction in UPCR from baseline
• Percent of subjects experiencing specified eGFR decline or end stage kidney disease (ESKD) [ Time Frame: Up to week 136 or approximately 2.6 years ]
  Percent of subjects experiencing at least a 30% reduction in eGFR or reach ESKD during the study
• Percent of subjects experiencing specified eGFR decline or end stage kidney disease [ Time Frame: Up to week 136 or approximately 2.6 years ]
  Percent of subjects experiencing at least a 40% reduction in eGFR or reach ESKD during the study

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Atrasentan in Patients With IgA Nephropathy
• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Double-blind

Primary Purpose: Treatment

Condition

• IgA Nephropathy
• Immunoglobulin A Nephropathy

Intervention

• Drug: Atrasentan
  Film-coated tablet
  Other Names:

  • CHK-01
  • Atrasentan Hydrochloride
  • ABT-627
• Drug: Placebo
  Film-coated tablet

Study Arms

• 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.

  Intervention: Drug: Atrasentan
• Placebo Comparator: Placebo
  Double-blind Period: Once daily oral administration of placebo for 132 weeks
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 20, 2022): 380
• Original Estimated Enrollment (submitted: September 28, 2020): 320
• Estimated Study Completion Date: December 1, 2026
• Actual Primary Completion Date: September 7, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, China, Colombia, France, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, New Zealand, Poland, Portugal, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Czechia, Ireland

Administrative Information

• NCT Number: NCT04573478
• Other Study ID Numbers: CHK01-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Chinook Therapeutics, Inc. ( Chinook Therapeutics U.S., Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Chinook Therapeutics U.S., Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Chinook Therapeutics, Inc.
• Verification Date: May 2024