Completed

This study has been completed.

Atrasentan in Patients With IgA Nephropathy (ALIGN)

NCT04573478Sponsor: Chinook Therapeutics, Inc.Matthew WeirMatthew Weir

About This Study

The ALIGN study is a Phase 3, randomized, double-blind trial evaluating the efficacy and safety of atrasentan, a selective endothelin A receptor antagonist, in patients with biopsy-proven IgA nephropathy at risk of progressive renal function loss. Participants receive 0.75 mg of atrasentan or placebo daily for 132 weeks while maintained on a maximally tolerated, stable dose of a RAS inhibitor. The study population includes a primary cohort of approximately 320 patients and a separate stratum for those on stable SGLT2i therapy. The primary endpoint is the change in proteinuria as measured by UPCR, with secondary outcomes assessing kidney function via eGFR slope and overall safety.

Who Can Participate?

✓ 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.