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Kidney Week

Abstract: INFO12-SA

Rationale and Design of a Phase 2b Study of Verinurad Plus Allopurinol in Patients with CKD and Hyperuricemia

Session Information

  • Informational Posters - III
    November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

Authors

  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Greene, Tom, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States
  • Stack, Austin G., University of Limerick, Limerick, Ireland
  • Terkeltaub, Robert, University of California San Diego, La Jolla, California, United States
  • Perl, Shira, AstraZeneca R&D, Gaithersburg, Maryland, United States
  • Dronamraju, Nalina, AstraZeneca R&D, Gaithersburg, Maryland, United States
  • Erlandsson, Fredrik, AstraZeneca R&D, Mölndal, Sweden
  • Perkovic, Vlado, The George Institute Australia, Newtown, New South Wales, Australia
Description

Background:
Elevated serum uric acid (sUA) predicts CKD progression, but a relationship between sUA and kidney outcomes is not proven. In a phase 2a study (NCT03118739), verinurad+febuxostat lowered sUA by 60% and albuminuria by 39% at Wk 12 in patients (pts) with T2DM and hyperuricemia. This phase 2b randomized, placebo-controlled study will examine the effect of intensive urate lowering on kidney function (estimated glomerular filtration rate [eGFR]) and albumin/creatinine ratio (ACR) in pts with CKD (±T2DM) and hyperuricemia and provide insight into potential treatment benefit.
Methods:
Pts will be ≥18 y with CKD, with eGFR ≥25 mL/min/1.73 m2, ACR 30–5000 mg/g and sUA ≥6.0 mg/dL. 725 pts will be randomized equally to high, intermediate or low dose verinurad+allopurinol, allopurinol or placebo (Figure). An 8-wk dose-titration period will precede a ≥52-wk treatment stage; all pts will receive treatment until the last randomized pt has been treated for 60 wks. Primary endpoint is change from baseline (BL) in ACR at 6 months. Secondary endpoints include changes in ACR and sUA from BL at 6 and 12 months. A Bayesian analysis will quantify the joint implications of estimated treatment effects on ACR and eGFR slope for clinical benefit. The effects of verinurad+allopurinol combination on measurable structural and functional kidney changes will be assessed using MRI and various cardio-renal biomarkers.
Conclusion:
This study will assess the clinical effect of verinurad+allopurinol on kidney function in CKD pts with hyperuricemia, and if intensive urate lowering confers renoprotection beyond SoC. Results are expected by 2022.

Funding

  • AstraZeneca