ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO242

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

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States
  • Pergola, Pablo E., Renal Associates, PA, San Antonio, Texas, United States
  • Fischbach, Bernard V., Dallas Nephrology Associates, Fort Worth, 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., University of Alabama Birmingham, Birmingham, Alabama, United States
  • Gross, Oliver, University Medicine Goettingen, Goettingen, Germany
Background

A Phase 2/3 trial (CARDINAL, NCT03019185) was initiated to determine if bardoxolone methyl (BARD) will improve eGFR in patients with Alport syndrome (AS). Primary efficacy analyses from the Phase 2 portion of the trial previously showed that BARD increased eGFR by 13.4 mL/min/1.73 m2 (n=30, p<0.0001) after 12 weeks of treatment. Interim results for patients who have completed 48 weeks of treatment are described herein.

Methods

The Phase 2 open-label portion of the trial enrolled 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, and urinary albumin to creatinine ratio (UACR) ≤ 3500 mg/g. Patients received once-daily doses of BARD at 5 mg and dose-escalated to 20 mg or 30 mg (for patients with baseline UACR > 300 mg/g), as tolerated. Following the Week 48 visit, patients stopped receiving BARD during a 4-week withdrawal period before completing the Week 52 visit.

Results

As of May 15, 2018, 13/30 (43%) of the enrolled patients had received 48 weeks of treatment, and 8 patients had Week 52 data. Treatment with BARD produced mean increases in eGFR of 14.0 mL/min/1.73 m2 at Week 48 (n=13; 95% CI: 9.5 to 18.5; p<0.0001). Moreover, after one year of treatment with BARD and withdrawal of drug, eGFR remained above baseline with mean increases in eGFR of 5.6 mL/min/1.73 m2 at Week 52 (n=8; 95% CI: 0.3 to 10.9, p=0.04). Geometric mean UACR also increased, but log UACR/eGFR ratios were unchanged from baseline. The most commonly reported AE was muscle spasms, which were generally mild to moderate in severity, with no evidence of muscle toxicity. No drug-related serious AEs or discontinuations had been reported in the ongoing Phase 2 portion of the trial at the time of data cutoff.

Conclusion

In patients with AS, BARD was generally well tolerated and produced improvements in kidney function that were sustained for up to one year and remained significantly above baseline following treatment withdrawal. The Phase 3 double-blind, randomized, placebo-controlled portion of the trial that will enroll up to 150 patients is underway.

Funding

  • Commercial Support