Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia.

Abstract

BACKGROUND:

Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4-62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia.

METHODS:

Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30-5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months.

CONCLUSIONS:

This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

• Authors: Hiddo J L Heerspink, Austin G Stack, Robert Terkeltaub, Tom A Greene, Lesley A Inker, Magnus Bjursell, Shira Perl, Tord Rikte, Fredrik Erlandsson, Vlado Perkovic
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 37 Issue 8 Pg. 1461-1471 (07 26 2022) ISSN: 1460-2385 [Electronic] England
• PMID: 34383954 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.

Chemical References

• Naphthalenes
• Propionates
• Pyridines
• verinurad
• Allopurinol
• Aluminum Oxide

Topics

• Adult
• Albuminuria (complications)
• Allopurinol (therapeutic use)
• Aluminum Oxide (pharmacology, therapeutic use)
• Clinical Trials, Phase II as Topic
• Demography
• Diabetes Mellitus, Type 2 (complications)
• Glomerular Filtration Rate
• Humans
• Hyperuricemia (drug therapy, etiology)
• Naphthalenes
• Propionates
• Pyridines
• Randomized Controlled Trials as Topic
• Renal Insufficiency, Chronic (complications, drug therapy)