Kidney Week

Abstract: FR-PO1059

Vascular Adhesion Protein-1 Inhibitor (VAP-1i) Reduces Albuminuria in Diabetic Kidney Disease

Session Information

• Late-Breaking Clinical Trial Posters
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Diabetes

• 502 Diabetes Mellitus and Obesity: Clinical

Authors

• de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands

Dick de Zeeuw,

• Renfurm, Ronny, Astellas Pharma Europe B.V., Leiden, Netherlands

Ronny Renfurm,

• Larsson, Tobias E., Astellas Pharma Europe B.V., Leiden, Netherlands

Tobias E. Larsson,

Group or Team Name

• ALBUM investigators

Background

Many diabetic kidney disease (DKD) patients treated with Angiotensin Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) have residual albuminuria and high risk for disease progression. We investigated the efficacy of a novel and specific VAP-1i, ASP8232, for reducing albuminuria on top of ACEi or ARB treatment in DKD. VAP-1 is an amine-oxidase with pro-inflammatory and pro-oxidative stress actions that is elevated and predicts cardiovascular risk in diabetes.

Methods

ALBUM was a randomized, double-blind, placebo-controlled, Phase 2 study in 45 European centers, enrolling 125 patients with type 2 diabetes and DKD. Inclusion criteria included Urinary Albumin Creatinine Ratio (UACR) >200 mg/g, eGFR 25-75 ml/min/1.73 m², and stable ACEi or ARB and anti-diabetic treatment for >3 months. After a 5-week screening/run-in, patients were randomized to ASP8232 40mg or placebo once daily for 12 weeks. Primary endpoint was change from baseline to end of treatment in first morning void (FMV) UACR. Secondary endpoint was change in 24-h albuminuria. A sample size of 110 was sufficient to detect 30% UACR reduction vs placebo with 80% power at a significance level of 5%.

Results

Of 406 patients screened, 125 were randomized and 120 were included in the analysis. Mean age was 69 yr, BMI 32 kg/m², HbA_1c 7.5%, BP 139/75 mmHg, eGFR 39.7 ml/min/1.73m², UACR 715 mg/g. Randomization was balanced. Use of ACEi (48.3% vs 53.3%), ARB (50.0% vs 43.3%), and combination (1.7% vs 3.3%) therapy was similar among ASP8232 vs placebo groups, respectively. Effects of ASP8232 vs placebo are shown in the table. ASP8232 reduced UACR_FMV by 19.5% (p=0.033), albuminuria_FMV by 26% (p=0.004), and 24h albuminuria by 20.0% (p=0.094). Reduction in UACR of >30% was observed in 37% of ASP8232 vs 22% of placebo patients (p=0.109). ASP8232 was safe and well tolerated; no serious drug-related adverse events were reported.

Conclusion

The VAP-1i ASP8232 yielded a clinically meaningful reduction of residual albuminuria in patients with DKD on stable ACEi/ARB treatment compared with placebo after 12 weeks of treatment.

Funding

• Commercial Support – Astellas Pharma Inc