A Study to Evaluate Finerenone on Clinical Efficacy and Safety in Patients With Heart Failure Who Are Intolerant or Not Eligible for Treatment With Steroidal Mineralocorticoid Receptor Antagonists

Study Overview
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Brief Summary
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Finerenone will be compared to placebo to determine efficacy and safety of treatment in patients heart failure and reduced ejection fraction (HFrEF) who are intolerant or ineligible to receive treatment with steroidal mineralocorticoid receptor antagonist (sMRA).

Detailed Description
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This is an international, randomized, double-blind, placebo-controlled trial of finerenone for the treatment of heart failure patients with reduced ejection fraction.

Official Title
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A Randomized, Double-blind, Placebo-controlled Pragmatic Study to Evaluate Finerenone on Clinical Efficacy and Safety in Patients With Heart Failure and Reduced Ejection Fraction Who Are Intolerant of or Not Eligible for Treatment With Steroidal Mineralocorticoid Receptor Antagonists (FINALITY-HF)

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Finerenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide electronic or written informed consent, either personally or through a legally authorized representative Age ≥18 years or legal age of majority Symptomatic HFrEF per protocol defined criteria Not on sMRA due to history of intolerance, contraindication, or ineligibility for treatment Negative pregnancy test and agreement to use adequate contraception during trial (female participants only) Exclusion Criteria: Treatment with non-steroidal MRA (nsMRA) eGFR < 25 mL/min/1.73m² and / or serum/plasma potassium > 5.0 mmol/L Type 1 acute myocardial infarction, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days or planned Prior or planned heart transplant Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of heart failure Symptomatic bradycardia or second- or third-degree heart block without a pacemaker Cardiomyopathy due to known acute inflammatory heart disease, infiltrative diseases, accumulation diseases, muscular dystrophies, cardiomyopathy with reversible causes, hypertrophic obstructive cardiomyopathy, complex congenital heart disease, or pericardial constriction Probable alternative cause of participant's HF Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors, or moderate or potent CYP3A4 inducers Any other condition or therapy which would make the participant unsuitable for the study Concurrent participation in another interventional clinical study using an investigational agent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Finerenone<br> | Drug: Finerenone<br>* Oral finerenone.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching oral placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurrence of cardiovascular (CV) death or HF event. | - Time to first CV death or HF event with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Number of serious adverse events | - Serious adverse events (excluding efficacy endpoints) with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Number of adverse events leading to discontinuation of study drug. | - Number of adverse events leading to discontinuation of investigational product with finerenone compared to placebo. | Ongoing, up to  30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timing and occurrence of total HF events and CV deaths. | - Timing and occurrence of total (first and subsequent) HF events and CV deaths with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Change in Total Symptom Score on the Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS) at Day 180. | - Change in KCCQ-TSS with finerenone compared to placebo. | 180 days | 
| Time to first occurrence of composite kidney endpoint. | Composite endpoint: Estimated glomerular filtration rate (eGFR) ≥50% relative to baseline over at least 4 weeks, or sustained eGFR decline to <15 ml/min/1.73 m2 or the initiation of long-term dialysis or kidney transplantation with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Time to CV death. | - Time to CV death with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Time to death from any cause. | - Time to all-cause mortality with finerenone compared to placebo. | Ongoing, up to  30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reduced ejection fraction, Symptomatic heart failure