Finerenone for Regression of Albuminuria in Type 2 Diabetes With Chronic Kidney Disease

Overview

This is a multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for the early regression of albuminuria in adults with type 2 diabetes mellitus and chronic kidney disease (eGFR \>= 30 mL/min/1.73 m\^2 and UACR 30-2000 mg/g) who are already receiving a maximum tolerated dose of an ACE inhibitor or ARB. A total of 148 participants are randomized 1:1, stratified by baseline UACR (\<300 vs \>=300 mg/g), to oral finerenone (10 or 20 mg once daily, titrated by serum potassium and eGFR) or matching placebo, on top of standard background therapy, for 180 days, followed by a 30-day off-treatment follow-up. Albuminuria regression is defined as both an improvement in Kidney Disease: Improving Global Outcomes albuminuria category, from A3 to A2 or A1, or from A2 to A1, and a more than 30% reduction in urinary albumin-to-creatinine ratio from baseline. The outcome will be reported as the percentage of participants meeting this definition at Day 180.

Background and rationale: Finerenone is an oral, highly selective nonsteroidal mineralocorticoid receptor antagonist approved in China for the treatment of chronic kidney disease associated with type 2 diabetes (with albuminuria). In the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone added to a maximum tolerated dose of a renin-angiotensin system inhibitor significantly and durably reduced the urine albumin-to-creatinine ratio (UACR) and lowered the risk of kidney and cardiovascular events, with a manageable hyperkalemia risk. A meaningful reduction in albuminuria is an established early surrogate for slowing CKD progression and reducing cardiovascular risk. This study evaluates whether finerenone can achieve early regression of albuminuria in patients with type 2 diabetes and CKD. Design: This is a multicenter, randomized, double-blind, placebo-controlled trial conducted at up to 12 sites in China. A planned 148 participants are allocated 1:1 to finerenone or matching placebo using central, block randomization (interactive response technology), stratified by baseline UACR (\<300 vs \>=300 mg/g). Participants and investigators are blinded; placebo tablets are identical in appearance to finerenone, and intervention-period UACR samples are assayed centrally after study completion to preserve blinding. Population: Eligible participants are adults with type 2 diabetes and CKD (eGFR \>= 30 mL/min/1.73 m\^2 and UACR 30-2000 mg/g) who have received a maximum tolerated dose of an ACE inhibitor or ARB for at least 90 days and have serum potassium \<= 5.0 mmol/L. Intervention and dose titration: The starting dose is determined by screening eGFR: 10 mg once daily for 30 \<= eGFR \< 60 mL/min/1.73 m\^2, or 20 mg once daily for eGFR \>= 60 mL/min/1.73 m\^2. The dose is up-titrated to 20 mg, maintained, interrupted, or down-titrated to 10 mg based on serum potassium and eGFR at scheduled and, if needed, unscheduled safety visits. Treatment continues for 180 days. Visit schedule: a screening period (Day -30 to -1; V1); a treatment period ; and an off-treatment follow-up at Day 210 +/- 5 (V7). Unscheduled safety visits and early-discontinuation visits are performed as needed. Endpoints: The primary endpoint is the albuminuria regression rate at 180 days, defined as a reduction in UACR KDIGO albuminuria category (A3 to A2 or A1, or A2 to A1) together with a \>=30% reduction in UACR from baseline. Secondary endpoints include the change in UACR, the rate of regression to normoalbuminuria, the proportions achieving \>=30/40/50% UACR reduction, KDIGO GFR-Albuminuria category improvement, the change in UACR 30 days after discontinuation, the change in eGFR slope, and the change in blood pressure. Safety endpoints include adverse events, serious adverse events, and adverse events of special interest (notably serum potassium changes and hyperkalemia). Exploratory endpoints also included.