Abstract: PO1303
Patient Global Impression of Change in Patients with Alport Syndrome in the CARDINAL Phase 3 Trial
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - I
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
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.
| Placebo | Bardoxolone Methyl | Difference Between Groups | |
| Week 48 Mean ± SE | 3.76 ± 0.10 | 3.59 ± 0.12 | -0.17 ± 0.149 (p = 0.26) |
| Week 100 Mean ± SE | 3.90 ± 0.13 | 3.51 ± 0.14 | -0.39 ± 0.186 (p = 0.04) |
Funding
- Commercial Support – Reata Pharmaceuticals