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

• CKD: Clinical, Outcomes, Trials - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

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

Authors

• Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States

Geoffrey A. Block,

• Pergola, Pablo E., Renal Associates, PA, San Antonio, Texas, United States

Pablo E. Pergola,

• Fischbach, Bernard V., Dallas Nephrology Associates, Fort Worth, Texas, United States

Bernard V. Fischbach,

• Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States

Lesley Inker,

• McCullough, Peter A., Baylor University Medical Center , Dallas, Texas, United States

Peter A. McCullough,

• Chin, Melanie, Reata Pharmaceuticals, Irving, Texas, United States

Melanie Chin,

• Meyer, Colin John, Reata Pharmaceuticals, Irving, Texas, United States

Colin John Meyer,

• Rheault, Michelle N., University of Minnesota, Minneapolis, Minnesota, United States

Michelle N. Rheault,

• Kashtan, Clifford E., University of Minnesota, Minneapolis, Minnesota, United States

Clifford E. Kashtan,

• Warnock, David G., University of Alabama Birmingham, Birmingham, Alabama, United States

David G. Warnock,

• Gross, Oliver, University Medicine Goettingen, Goettingen, Germany

Oliver Gross,

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 – Reata Pharmaceuticals