Kidney Week

Abstract: SA-PO146

Primary Efficacy Analyses from a Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients with Type 1 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Silva, Arnold L., Boise Kidney & Hypertension Institute, Meridian, Idaho, United States

Arnold L. Silva,

• Awad, Ahmed M., Clinical Research Consultants, LLC, Kansas City, Missouri, United States

Ahmed M. Awad,

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

Geoffrey A. Block,

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

Melanie Chin,

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

Colin John Meyer,

• Schroeder, Kevin, Ohio Kidney Consultants, Columbus, Ohio, United States

Kevin Schroeder,

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

Pablo E. Pergola,

Background

Bardoxolone methyl (BARD) has been shown to significantly increase eGFR in patients with CKD and type 2 diabetes or Alport syndrome suggesting that the anti-inflammatory and anti-fibrotic effects of BARD may target the common pathways contributing to GFR loss in multiple forms of CKD. As a result, a Phase 2 trial (PHOENIX, NCT03366337) was initiated to test the hypothesis that BARD will improve kidney function in patients with CKD due to type 1 diabetes mellitus (T1DM) as well as other forms of CKD.

Methods

The Phase 2 open-label, multicenter study enrolled a cohort of patients T1DM confirmed by fasting C-peptide levels. Eligible patients were 18 to 65 years of age with eGFR values between 30 to 90 mL/min/1.73 m² and urine albumin to creatinine ratio (UACR) ≤ 2500 mg/g. Patients received BARD at an initial dose of 5 mg, dose-escalated to 20 mg (for patients with baseline UACR ≤ 300 mg/g) or to 30 mg (for patients with baseline UACR > 300 mg/g) and were treated for 12 weeks. The primary efficacy endpoint was the change from baseline eGFR after 12 weeks of treatment. Interim results for the cohort enrolling patients with T1DM are described herein.

Results

At data cutoff on May 15^th, 2018, 3/19 (16%) of the enrolled patients with T1DM had completed the study. From a mean (± SE) baseline eGFR of 68.2 ± 3.8 mL/min/1.73 m², BARD treatment resulted in a significant increase from baseline in eGFR of 7.9 ± 2.9 mL/min/1.73 m² (p=0.008) at Week 12. No patients have discontinued from the study and no serious AEs considered related to BARD have been reported in this ongoing trial.

Conclusion

BARD was generally well tolerated and significantly increased eGFR in patients with T1DM. In patients with other forms of CKD, short term eGFR increases with BARD are predictive of durable eGFR improvements and additional studies are needed to study the longer-term effects of BARD on eGFR in T1DM.

Funding

• Commercial Support –