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Kidney Week

Abstract: PO1300

Interim Analysis of the EAGLE Trial: An Open-Label Study to Assess the Long-Term Safety and Tolerability of Bardoxolone Methyl in Patients with Alport Syndrome

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
  • Appel, Gerald B., Columbia University Irving Medical Center, New York, New York, United States
  • Chin, Melanie, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Fischbach, Bernard V., Dallas Nephrology Associates, Dallas, Texas, United States
  • Knebelmann, Bertrand, Structure Federative de Recherche Necker, Paris, Île-de-France, France
  • Lieberman, Kenneth V., Hackensack Meridian School of Medicine, Nutley, New Jersey, United States
  • Meyer, Colin John, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Nozu, Kandai, Kobe Daigaku, Kobe, Hyogo, Japan
  • Packham, David K., The University of Melbourne Medicine at Royal Melbourne Hospital, Parkville, Victoria, Australia
  • Rizk, Dana, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Silva, Arnold L., Boise Kidney and Hypertension Institute, Meridian, Idaho, United States
  • Spinowitz, Bruce S., New York Presbyterian Queens Hospital, Flushing, New York, United States
  • Sprague, Stuart M., NorthShore Medical Group, Evanston, Illinois, United States
  • Torra, Roser, Universitat Autonoma de Barcelona, Barcelona, Catalunya, Spain
  • Zaoui, Philippe, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, Rhône-Alpes, France
Background

Alport syndrome is a rare genetic disease affecting up to 60,000 persons in the US.

Methods

EAGLE (NCT03749447) is an ongoing, international, multi-center, open-label, extended access trial evaluating the longer-term safety and tolerability of bardoxolone methyl (bardoxolone) in patients with Alport syndrome who completed a prior qualifying clinical trial (CARDINAL Phase 2 and 3; NCT03019185). At baseline patients were 12 to 70 years old with eGFR 30 to 90 mL/min/1.73 m2 and UACR ≤ 3500 mg/g. Patients receive bardoxolone daily and dose is escalated up to 20 mg or 30 mg (for patients with UACR > 300 mg/g).

Results

As of data cutoff (01/18/2021), 96 patients were enrolled in the EAGLE study, including 79 patients from CARDINAL Phase 3 (placebo: n=46, Bard: n=33), and 17 patients who received Bard in CARDINAL Phase 2. Mean age was 42 years, and 8 (8%) patients were <18. At baseline, mean eGFR was 58.2 ± 21.4 mL/min/1.73 m2 and mean UACR was 183 ± 40 mg/g.

Increases in eGFR were seen in patients who previously received placebo and initiated Bard treatment in EAGLE. Patients who previously received Bard for two years in CARDINAL also continued to experience mean eGFR increases in their third year of treatment.

Bard has generally been well tolerated, with no deaths or drug-related severe adverse events (SAEs) reported in EAGLE to date. No drug-related cardiac SAEs were reported and no changes in blood pressure were observed. Nearly all (94%) adverse events were mild to moderate.

Conclusion

In EAGLE, Bard increased eGFR in patients with Alport syndrome, and increases observed in CARDINAL were sustained in the third year of treatment. To date, the longer-term safety profile of Bard is similar to that observed in the CARDINAL trial.

Mean ± SD eGFR Change
(mL/min/1.73 m2)
Week 12Week 24Week 48
Placebo to Bard (n=46)n=28
12.4 ± 11.8
n=14
9.3 ± 14.7
n=8
8.4 ± 11.5
Bard to Bard (n=50)n=39
8.8 ± 15.3
n=30
9.9 ± 14.0
n=19
7.3 ± 8.8

Funding

  • Commercial Support