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Abstract: FR-OR62

Effect of Isuzinaxib, Pan NOX Inhibitor in Patients With Type 2 Diabetes and CKD in a Randomized, Double Blind, Placebo Controlled Phase 2 Trial

Session Information

  • High-Impact Clinical Trials
    November 04, 2022 | Location: W415 Valencia, Orange County Convention Center‚ West Building
    Abstract Time: 10:45 AM - 11:00 AM

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Cha, Dae R., Korea University College of Medicine and School of Medicine, Seoul, Korea (the Republic of)
  • Wittmann, Istvan, Faculty of Medicine, University of Pécs, Pécs, Hungary
  • Moon, Sung Hwan, Aptabio Therapeutics Inc., Yongin-si, Gyeonggi-do, Korea (the Republic of)
  • Lee, Soo Jin, Aptabio Therapeutics Inc., Yongin-si, Gyeonggi-do, Korea (the Republic of)
Background

Isuzinaxib (APX-115), a novel inhibitor of pan NOX; oxidative stress modulator was investigated a kidney outcome in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) compared with Placebo.

Methods

In this phase 2 trial, patients with T2DM and CKD were randomized (1:1) from 4 countries in Europe and treated with Isuzinaxib 400mg QD or Placebo for 12 weeks orally. Eligible patients had a urinary albumin to creatinine ratio (UACR) of 200 to 3000 mg/g cr, an estimated glomerular filtration rate (eGFR) of 30 to 90 mL/min/1.73 m2 and stable treatments with renin angiotensin system inhibitors (ACEi or ARB). The primary endpoint was mean change in UACR at Week 12. The secondary outcomes assessed safety, tolerability, pharmacokinetics of Isuzinaxib and change in biomarkers compared with Placebo. (NCT04534439)

Results

Mean age of patients was 63 years and 62.9% were male. At baseline, mean eGFR was 65.1 and 65.6 mL/min/1.73 m2 and mean UACR was 978 and 853 mg/g cr in Isuzinaxib (N=68) and Placebo (N=72), respectively. Mean change of UACR was -21% in Isuzinaxib and -2.5% in Placebo, at Week 12. In group with baseline eGFR <45, Isuzinaxib reduced UACR -36%, whereas increased 11% in Placebo (P=0.0197). Interestingly, KIM-1 was reduced significantly in Isuzinaxib (P=0.0128).
In an ad-hoc analysis, patients with Isuzinaxib stable state in pharmacokinetics data depending on its drug compliance, showed significant UACR (-31.2%, P=0.0165) and UPCR (Urine protein to creatinine ratio, -23.8%, P=0.045) reductions compared with Placebo.
Overall treatment-emergent adverse events were balanced between groups. There was no clinically relevant safety finding in use of Isuzinaxib.

Conclusion

Isuzinaxib resulted in anti-albuminuric effect and was safe and well tolerable in patients with T2DM and CKD. The results demonstrate first clinical evidence by NADPH oxidase (NOX) inhibitors contributing to oxidative stress in patients with T2DM and CKD.

Funding

  • Commercial Support