Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease

Chronic Kidney Disease Clinical Trial

— FIDELIO-DKD  

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Event-driven Phase 3 Study to Investigate the Safety and Efficacy of Finerenone, in Addition to Standard of Care, on the Progression of Kidney Disease in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02540993
• Other study ID #: 16244
• Secondary ID: 2015-000990-11
• Status: Completed
• Phase: Phase 3
• Start date: September 17, 2015
• Est. completion date: April 14, 2020

Study information

• Verified date: July 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to demonstrate whether, in addition to standard of care, finerenone is superior to placebo in delaying the progression of kidney disease, as measured by the composite endpoint of time to first occurrence of kidney failure, a sustained decrease of estimated glomerular filtration rate (eGFR) ≥40% from baseline over at least 4 weeks, or renal death.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5734
• Est. completion date: April 14, 2020
• Est. primary completion date: April 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men or women =18 years of age

• Type 2 diabetes mellitus (T2D) as defined by the American Diabetes Association

• Diagnosis of chronic kidney disease (CKD) with at least one of the following criteria at run-in and screening visits:

• persistent high albuminuria (UACR =30 to <300 mg/g in 2 out of 3 first morning void samples) and estimated glomerular filtration rate (eGFR) =25 but <60 mL/min/1.73 m² (CKD EPI) and presence of diabetic retinopathy or

• persistent very high albuminuria (UACR =300 mg/g in 2 out of 3 first morning void samples) and eGFR =25 to <75 mL/min/1.73 m² (CKD-EPI)

• Prior treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as follows:

• For at least 4 weeks prior to the run-in visit, subjects should be treated with either an ACEI or ARB, or both

• Starting with the run-in visit, subjects should be treated with only an ACEI or ARB

• For at least 4 weeks prior to the screening visit, subjects should be treated with the maximum tolerated labeled dose (but not below the minimal labeled dose) of only an ACEI or an ARB (not both) preferably without any adjustments to dose or choice of agent or to any other antihypertensive or antiglycemic treatment

• Serum potassium =4.8 mmol/L at both the run-in and the screening visit

Exclusion Criteria:

• Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis

• Uncontrolled arterial hypertension (ie, mean sitting systolic blood pressure (SBP) =170 mmHg, sitting diastolic blood pressure (DBP) =110 mmHg at run-in visit, or mean sitting SBP =160 mmHg, sitting DBP =100 mmHg at screening)

• Glycated hemoglobin (HbA1c) >12%

• Mean SBP < 90 mmHg at the run-in visit or at the screening visit

• Clinical diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association [NYHA] class II - IV) at run-in visit (class 1A recommendation for mineralcorticoid receptor antagonists [MRAs])

• Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for worsening heart failure, in the last 30 days prior to the screening visit

• Dialysis for acute renal failure within 12 weeks of run-in visit

• Renal allograft in place or scheduled within next 12 months from the run-in visit

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Finerenone (BAY94-8862)
Oral tablet; starting dose at 10 mg for subjects with an eGFR between 25 to < 60 mL/min/1.73m² at the Screening Visit; starting dose at 20 mg for subjects with an eGFR = 60 mL/min/1.73m² at the Screening Visit; dose could be up-titrated from Month 1 onwards or down-titrated at any time during the study; once daily in the morning, until the trial was completed provided there were no safety grounds for discontinuing treatment
• Placebo
Matching placebo, oral tablet, once daily in the morning, until the trial was completed provided there were no safety grounds for discontinuing treatment

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Philippines,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (3)

Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Nowack C, Kolkhof P, Ferreira AC, Schloemer P, Filippatos G; on behalf of the FIDELIO-DKD study investigators; FIDELIO-DKD study investigators. Design and Baseline Characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease Trial. Am J Nephrol. 2019;50(5):333-344. doi: 10.1159/000503713. Epub 2019 Oct 25. — View Citation

Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23 — View Citation

Filippatos G, Anker SD, Agarwal R, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Schloemer P, Tornus I, Joseph A, Bakris GL; FIDELIO-DKD Investigators. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. Circula — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR =40% From Baseline Over at Least 4 Weeks, or Renal Death	Count of participants and time from randomization to the first occurrence of the primary renal composite outcome, onset of kidney failure, a sustained decrease of eGFR =40% from baseline over at least 4 weeks, or renal death were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.	From randomization up until the first occurrence of the primary renal composite endpoint, or censoring at the end of the study, with an average follow-up time of 32 months
Secondary	The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, or Hospitalization for Heart Failure	Count of participants and time from randomization to the first occurrence of the key secondary cardiovascular (CV) composite outcome, CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.	From randomization up until the first occurrence of the key secondary CV composite endpoint, or censoring at the end of the study, with an average of 32 months
Secondary	All-cause Mortality	Count of participants and time from randomization until death due to any cause were evaluated. Number of participants with outcome death is reported as descriptive result and hazard ratio is reported as statistical analysis. Number of participants with outcome death reported here includes deaths occurred after randomization until the end of the study visit. Deaths after end of study visit are not included in this table.	From randomization up until death due to any cause, or censoring at the end of the study visit, with an average of 32 months
Secondary	All-cause Hospitalization	Count of participants and time from randomization to the first occurrence of a hospitalization event were evaluated. Number of participants with the event is reported as descriptive result and hazard ratio is reported as statistical analysis.	From randomization up until the first occurrence of the hospitalization due to any cause, or censoring at the end of study, with an average of 32 months
Secondary	Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline to Month 4	First morning void urine samples were collected to evaluate the urinary albumin-to-creatinine ratio (UACR). Month 4 was the visit closest to day 120 within a time window of 120 ± 30 days after randomization. If no measurements were available in this time window, the participant was excluded from this analysis. Ratio of UACR at Month 4 to UACR at baseline is reported as the change.	From baseline up until Month 4
Secondary	The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of =57% From Baseline Over at Least 4 Weeks, or Renal Death	Count of participants and time from randomization to the first occurrence of the secondary renal composite outcome, onset of kidney failure, a sustained decrease in eGFR of =57% from baseline over at least 4 weeks, or renal death were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.	From randomization up until the first occurrence of the composite primary endpoint, or censoring at the end of the study, with an average of 32 months

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