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Kidney Week

Abstract: PO1303

Patient Global Impression of Change in Patients with Alport Syndrome in the CARDINAL Phase 3 Trial

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States
  • Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
  • Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Andreoli, Sharon P., Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, United States
  • Appel, Gerald B., Columbia University Irving Medical Center, New York, New York, United States
  • Bangalore, Sripal, NYU Langone Health, New York, New York, United States
  • Block, Geoffrey A., US Renal Care, Plano, Texas, United States
  • Chin, Melanie, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Gibson, Keisha L., University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
  • Goldsberry, Angie, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Iijima, Kazumoto, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo, Japan
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • Kashtan, Clifford E., University of Minnesota Health, Minneapolis, Minnesota, United States
  • Knebelmann, Bertrand, Institut Necker-Enfants Malades, Paris, Île-de-France, France
  • Mariani, Laura H., University of Michigan Medical School, Ann Arbor, Michigan, United States
  • Meyer, Colin John, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Nozu, Kandai, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo, Japan
  • O'Grady, Megan, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Silva, Arnold L., Boise Kidney and Hypertension Institute, Meridian, Idaho, United States
  • Stenvinkel, Peter, Karolinska Institutet, Stockholm, Stockholm, Sweden
  • Torra, Roser, Universitat Autonoma de Barcelona, Barcelona, Catalunya, Spain
  • Warady, Bradley A., Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
Background

Alport syndrome is a rare and serious inherited form of CKD affecting as many as 60,000 persons in the US with no specific therapies approved for its treatment.

Methods

An international, multicenter, double-blind, placebo-controlled, randomized Phase 3 trial (CARDINAL; NCT03019185) evaluated the safety and efficacy of bardoxolone methyl (Bard) in patients with Alport syndrome 12 to 70 years of age with baseline eGFR 30-90 mL/min/1.73 m2 and UACR≤ 3500mg/g. As an exploratory endpoint, the trial assessed patient global impression of change (PGIC), a non-disease specific 7-point scale that asks patients to rate how much their illness has changed as very much/much/minimally improved (1, 2, and 3 pts), no change (4 pts), or minimally/much/very much worse (5, 6, and 7 pts) after 48 and 100 weeks of treatment.

Results

A total of 157 patients were randomized to Bard (n=77) or placebo (n=80). In addition to significant on-treatment and off-treatment increases in mean eGFR relative to placebo (between-group differences of 7.7 ± 2.1 [p=0.0005] at Week 100 and 4.3 ± 1.9 mL/min/1.73 m2 [p=0.023] at Week 104, respectively), Bard improved PGIC scores relative to placebo (lower values) after 48 and 100 weeks. Categorical summaries also showed more patients randomized to bardoxolone (34%) reported their condition had improved compared to those on placebo (19%) after 100 weeks of treatment.

Conclusion

In CARDINAL, Bard significantly preserved eGFR in patients with Alport syndrome and also resulted in improvements in how patients evaluated their wellbeing.

 PlaceboBardoxolone MethylDifference Between Groups
Week 48 Mean ± SE 3.76 ± 0.103.59 ± 0.12-0.17 ± 0.149
(p = 0.26)
Week 100 Mean ± SE 3.90 ± 0.133.51 ± 0.14-0.39 ± 0.186
(p = 0.04)

Funding

  • Commercial Support