Efficacy and Safety of Finerenone for the Early Regression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 148
- 试验地点
- 13
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Age >= 18 years at the time of signing informed consent, male or female.
- •2. Type 2 diabetes mellitus.
- •3. Chronic kidney disease meeting BOTH of the following: eGFR (CKD-EPI) >= 30 mL/min/1.73 m^2, and UACR 30-2000 mg/g (mean of 3 measurements).
- •4. Serum potassium <= 5.0 mmol/L.
- •5. On a maximum tolerated dose of an ACE inhibitor or ARB for at least 90 days.
- •6. Treatment with an SGLT-2 inhibitor, GLP-1 receptor agonist, or other agents affecting UACR is permitted, but the type and dose must be stable for at least 30 days before screening.
排除标准
- •1. Type 1 diabetes, other specific types of diabetes, or gestational diabetes.
- •2. HbA1c >= 8.0%.
- •3. On renal replacement therapy.
- •4. Acute kidney injury within 180 days before the screening visit.
- •5. Hepatic impairment (Child-Pugh class C).
- •6. Blood pressure > 160/100 mmHg, or systolic blood pressure < 90 mmHg, at the screening visit.
- •7. Bilateral renal artery stenosis.
- •8. Known hypersensitivity to the study drug (active substance or excipients).
- •9. Treatment with finerenone within 60 days before screening.
- •10. Stroke, transient ischemic attack, acute coronary syndrome (myocardial infarction, CABG, PCI), or hospitalization for worsening heart failure within 90 days before the screening visit.
- •11. NYHA class II-IV heart failure.
- •12. Addison's disease.
- •13. Gastrointestinal surgery that may affect drug absorption.
- •14. Any other history, condition, therapy, or uncontrolled concomitant disease that makes the participant unsuitable for the study or unlikely to complete it (e.g., active malignancy or other disease with life expectancy < 12 months).
- •15. Treatment with a strong CYP3A4 inhibitor (e.g., itraconazole, clarithromycin, ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin, nefazodone), a strong CYP3A4 inducer (e.g., carbamazepine, phenytoin, phenobarbital, St. John's wort), or a moderate CYP3A4 inducer (e.g., efavirenz) that cannot be discontinued for at least 7 days before randomization.
- •16. Treatment with another mineralocorticoid receptor antagonist (e.g., spironolactone, eplerenone, esaxerenone) or a potassium-sparing diuretic (e.g., amiloride, triamterene) that cannot be discontinued for at least 60 days before the screening visit.
- •17. Biopsy-confirmed non-diabetic kidney disease (e.g., IgA nephropathy).
- •18. Immunosuppressive therapy, or glucocorticoid use by any route other than topical or inhaled, within the past 180 days.
- •19. Participation in another interventional clinical study or use of any investigational product within 90 days before randomization.
- •20. History of alcohol or drug abuse.
- •21. Women of childbearing potential who are pregnant, breastfeeding, intend to become pregnant, or are not using adequate contraception during the study.
- •22. Any other condition deemed by the investigator to make the participant unsuitable for the study.
研究者
Xiaomu Li
Director, Department of Endocrinology
First Affiliated Hospital of Zhejiang University