Abstract: FR-PO1053

Initial Data Report from “CARDINAL”: A Phase 2/3 Study of Bardoxolone Methyl in Patients with Alport Syndrome

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States
  • Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
  • Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States
  • McCullough, Peter A., Baylor University Medical Center, Dallas, Texas, United States
  • Chin, Melanie, Reata Pharmaceuticals, Irving, Texas, United States
  • Meyer, Colin John, Reata Pharmaceuticals, Irving, Texas, United States
  • Rheault, Michelle N., University of Minnesota, Minneapolis, Minnesota, United States
  • Kashtan, Clifford E., University of Minnesota, Minneapolis, Minnesota, United States
  • Warnock, David G., UAB, Birmingham, Alabama, United States
Background

In previous studies that enrolled over 2,600 patients, primarily including patients with CKD caused by type 2 diabetes, bardoxolone methyl (BARD) improved estimated GFR (eGFR) and inulin clearance. A Phase 2/3 trial (CARDINAL, NCT03019185) was initiated to test the hypothesis that BARD will improve eGFR in patients with Alport syndrome (AS).

Methods

The Phase 2 open-label portion of the study was designed to enroll 30 patients on stable RAAS blockade, ages 12 to 60 years, with confirmed diagnosis of AS, eGFR values from 30 to 90 mL/min/1.73 m2 [calculated using CKD-EPI or Bedside Schwartz (age < 18 years) equations], and urinary albumin to creatinine ratio (UACR) ≤ 3500 mg/g. Patients received BARD at 5 mg, to dose-escalate as tolerated to 10 mg at Week 2, 20 mg at Week 4, and for patients with baseline UACR > 300 mg/g, to 30 mg at Week 6. The primary efficacy endpoint was change from baseline in eGFR after 12 weeks of treatment. Interim results are described herein.

Results

30 patients were enrolled (mean age 44 years, 60% female, 73% X-linked AS). Data were extracted after the first 8 patients had received 12 weeks of treatment. From a mean baseline eGFR of 54.7 mL/min/1.73 m2, treatment with BARD produced mean improvements of 6.9 mL/min/1.73 m2 at Week 4 (n=19; p<0.0005), which further increased to 12.7 mL/min/1.73 m2 at Week 12 (n=8; p<0.00005), as of July 24th, 2017. Over 80% of patients demonstrated clinically meaningful improvement in eGFR of at least 3.0 mL/min/1.73 m2 by Week 8. eGFR improvements were associated with mean decreases in BUN, uric acid, and phosphorous. Median UACR increased, however, UACR/eGFR ratios were unchanged from baseline. Blood pressure was unchanged. The most commonly reported adverse event (AE) was muscle spasms, which were generally mild to moderate in severity, with no laboratory evidence of muscle toxicity. No patients have discontinued from the study and no serious AEs have been reported so far, in this ongoing trial.

Conclusion

BARD was generally well tolerated and improved kidney function in patients with AS. The Phase 3 double-blind, randomized, placebo-controlled portion of the trial that will enroll up to 150 patients has been initiated.

Funding

  • Commercial Support