821-P: Randomized Clinical Trial on the Renoprotective Effect of CU01-10in Patients with Diabetic Kidney Disease (DKD)

Abstract

Background: One of the leading causes of chronic kidney disease, DKD is associated with increased oxidative stress and chronic inflammation. CU01-10is dimethyl fumarate (DMF) which being developed for treatment of DKD. DMF attenuated renal fibrosis via the Nrf2-mediated inhibition of TGF-b/Smad3 signaling in an antioxidant response element independent manner in preclinical model, suggesting that DMF can be potentially effective against kidney damage. In this study, we investigated the efficacy and safety of CU01-10in patient with DKD. Methods: For this randomized, double-blinded phase 2a clinical trial for the efficacy and safety assessment, we enrolled 42 adults with DKD (estimated glomerular filtration rate (eGFR) 30 to 89 ml/min/1.73m2) with albuminuria to be treated with CU01-10 (120mg twice a day) or placebo. We measured the change from baseline in urine albumin creatinine ratio (uACR) and eGFR at 12 weeks for primary outcomes. Results: A total of 39 patients were evaluated for primary efficacy analysis. CU01-10group showed significant increase of eGFR (+ 3.80±8.72 ml/min/1.73m2at week 12, from baseline) , and there was a significant intergroup difference of eGFR at 6 and 12 weeks (p=0.0349 and p=0.0121, respectively) . CU01-10group was statistically significantly decreased in the mean ACR (p=0.0441) but not for placebo group (p=0.1336) , and after 12 weeks, CU01-10group (-39.65 mg/g) showed lower median uACR from the baseline than placebo (-16.90 mg/g) . In DMF group, no severe adverse events were reported during the trial and the most common adverse events were nausea (n=3) and skin flushing (n=3) . Conclusion: CU01-10showed an improvement of uACR and eGFR compared to placebo for patients with DKD, with no major drug-related adverse events. Disclosure J.Moon: None. K.Won: None. M.Kim: None. I.Lee: n/a. S.Kwon: None. J.Pyo: None. J.Kang: None. Y.Kwon: None. H.Seo: None.