Evaluation of Finerenone Efficacy and Safety in Heart Failure Patients with Reduced Ejection Fraction Intolerant or Ineligible for Steroidal Mineralocorticoid Receptor Antagonists
- Trial ID
- 2023-508875-35-00
- Protocol
- 202304CPC
- Sponsor
- Colorado Prevention Center
Trial statistics
Objectives
The primary objective of this study is to evaluate the **efficacy** and **safety** of **finerenone** in patients with **heart failure with reduced ejection fraction (HFrEF)** who are intolerant of or not eligible for treatment with steroidal mineralocorticoid receptor antagonists (sMRA). This is clinically relevant as it addresses a significant unmet need in the management of HFrEF, providing an alternative therapeutic option for patients who cannot tolerate or are contraindicated for sMRA therapy. The safety objective is to assess the safety and tolerability of finerenone, ensuring that the treatment is not only effective but also safe for long-term use in this patient population.
Participants
The clinical trial involves a total of **1860 participants** diagnosed with a **heart condition**, specifically focusing on individuals with heart failure with reduced ejection fraction (HFrEF). The study population includes both male and female subjects, aged 18 years and older, who are either intolerant of or not eligible for treatment with steroidal mineralocorticoid receptor antagonists (sMRA). Participants are required to have symptomatic HFrEF, classified as New York Heart Association (NYHA) class II to IV, with an ejection fraction of less than 40% confirmed by imaging within the past year. The trial population was selected based on specific inclusion criteria, including the requirement for a qualifying natriuretic peptide level and the absence of sMRA treatment due to intolerance or contraindications. The study also includes individuals from vulnerable populations, ensuring a comprehensive assessment of the efficacy and safety of finerenone. Participants of childbearing potential must have a negative pregnancy test and agree to use highly effective contraception throughout the study duration. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **finerenone** in patients with heart failure with reduced ejection fraction (HFrEF) who are intolerant of or not eligible for treatment with steroidal mineralocorticoid receptor antagonists (sMRA). The trial aims to assess the primary endpoint, which is the time to the first occurrence of cardiovascular death or a heart failure event. Secondary endpoints include differences in the timing and occurrence of cardiovascular death and heart failure events, changes in the Kansas City Cardiomyopathy Questionnaire – Total Symptom Score from baseline to Month 6, and time to all-cause death.
The trial is expected to commence recruitment in June 2025 and conclude by June 2028, with a maximum treatment period of 42 days for each participant. Participants will be administered **finerenone** or a placebo in the form of film-coated tablets, taken orally. The study will include an initial screening visit to confirm eligibility based on criteria such as age, symptomatic HFrEF, and intolerance or ineligibility for sMRA. Following randomization, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will occur after the treatment period to assess final outcomes and collect data on any adverse events.
Participant involvement is expected to last for the duration of the treatment period, with additional time allocated for follow-up assessments. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is conducted under strict ethical guidelines, ensuring that all participants provide written informed consent prior to enrollment. The study is not classified as a low-intervention trial and is categorized as a Phase 3 study, investigating the use of an already authorized medicinal product for a new indication.
Treatment
The clinical trial involves the administration of **finerenone**, an investigational medication, in the form of a **film-coated tablet**. The pharmaceutical product, identified as BAY 94-8862, is manufactured by Bayer AG. Finerenone is a chemical substance and is administered orally. The trial includes three different dosing regimens of finerenone: 10 mg, 20 mg, and 40 mg per day. The maximum daily dose is 40 mg, with a total maximum dose of 50,400 mg over a treatment period of 42 days. The dosing schedule is designed to evaluate the efficacy and safety of finerenone in participants with heart failure and reduced ejection fraction who are intolerant of or not eligible for treatment with steroidal mineralocorticoid receptor antagonists.
A placebo is also utilized in this study as a comparator treatment. The placebo is designed to match the finerenone film-coated tablet in appearance but does not contain any active pharmaceutical ingredient. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias in the assessment of the treatment's efficacy and safety.
Participant compliance with the dosing regimen is monitored throughout the study. Compliance is assessed through regular follow-up visits and the collection of unused medication. This ensures that the data collected on the efficacy and safety of finerenone is accurate and reliable. The trial is conducted under strict regulatory guidelines to ensure the safety and well-being of all participants.
Efficacy
The efficacy of **finerenone** in the clinical trial will be assessed using a primary endpoint and several secondary endpoints. The primary endpoint is defined as the time to the first occurrence of cardiovascular death or a heart failure event. Secondary endpoints include the timing and occurrence of total (first and recurrent) events of cardiovascular death and heart failure events, the timing and occurrence of total heart failure events, the change in the Kansas City Cardiomyopathy Questionnaire – Total Symptom Score (KCCQ-TSS) from baseline to Month 6, time to cardiovascular death, and time to all-cause death.
These efficacy parameters will be measured and collected at specified timepoints throughout the trial. The change in KCCQ-TSS will be assessed from baseline to Month 6, providing a patient-reported outcome measure of symptom improvement. The analysis of these endpoints will involve comparing treatment group differences in the timing and occurrence of events, as well as changes in symptom scores. The trial is designed to evaluate the efficacy of finerenone in patients with heart failure and reduced ejection fraction who are intolerant of or not eligible for treatment with steroidal mineralocorticoid receptor antagonists.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 years or legal age of majority if >18 years in the participant’s country of residence.
- Symptomatic HFrEF (must meet all criteria) • NYHA class II – IV symptoms at screening and randomization • Most recent ejection fraction <40% by imaging (e.g., echocardiogram, cardiac MRI, nuclear scan) within 12 months prior to screening • Qualifying natriuretic peptide level: Most recent local laboratory value within 14 days of randomization for patients with recent HHF (discharged within prior 10 days) or within 30 days for patients without recent HHF must meet the qualifying threshold below. If no value is available in the medical record, a local lab value must be obtained. Note: for participants treated with an angiotensin receptor/neprilysin inhibitor (ARNI) in the previous 4 weeks prior to natriuretic peptide measurement, only NTproBNP values should be used.
- Not on sMRA (i.e., spironolactone, eplerenone or canrenone/potassium canrenoate) due to documented history of being either intolerant, contraindicated (e.g., due to eGFR <30 mL/min/1.73m2) or considered ineligible for treatment with sMRA . • Intolerance is defined as at least one episode of hyperkalemia, or an episode of worsening kidney function, or an episode of sexual side effects or hypotension, each leading to drug interruption or discontinuation. • Ineligibility is in the opinion of the treating physician and/or investigator.
- Persons of childbearing potential can only be included in the study if a pregnancy test is negative at screening and if they agree to use highly effective contraception which is consistent with local regulations regarding the methods for contraception for the duration of the study.
- Provide written informed consent.
Exclusion Criteria
- Treatment with any MRA (e.g., spironolactone, eplerenone, finerenone, esaxerenone, apararenone) within 30 days prior to randomization; treatment with any MRA should not be interrupted for the purpose of enrollment into the study.
- Documented prior history of severe hyperkalemia (potassium ≥6.0 mmol/L and/or resulting in hospitalization or Emergency Department visit) in the setting of MRA use
- eGFR <25 mL/min/1.73m² and / or potassium >5.0 mmol/L at screening (most recent value within 14 days of randomization if acutely hospitalized or discharged within the last 10 days; within 30 days of randomization if no recent hospitalization). Note: eGFR and potassium should be repeated prior to randomization if renin-angiotensin system antagonist started or dose increased since most recent prior measurement
- Acute MI, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days prior to randomization or planned (note: pacemakers or implantable cardioverter defibrillators without resynchronization function are allowed)
- Prior heart transplant or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement) or currently using or plan for mechanical circulatory support, e.g., left ventricular assist device, intra-aortic balloon pump, or participants on mechanical ventilation or participants with planned outpatient inotropic support
- Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of heart failure (note: secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study)
- Symptomatic bradycardia or second- or third-degree heart block without a pacemaker
- Cardiomyopathy due to known acute inflammatory heart disease (e.g., acute myocarditis within 90 days prior to randomization), infiltrative diseases (e.g., amyloidosis), accumulation diseases (e.g., haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g., stress cardiomyopathy), known hypertrophic obstructive cardiomyopathy, complex (according to investigator`s judgement) congenital heart disease, or known pericardial constriction
- Probable alternative cause of participant’s HF symptoms that, in the opinion of the investigator, primarily accounts for patient’s symptoms; specifically, participants with severe pulmonary disease requiring home oxygen or chronic oral steroid therapy, primary pulmonary arterial hypertension at screening
- Concomitant treatment with: a) systemic potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g., itraconazole, ritonavir, indinavir, cobicistat, clarithromycin), or moderate CYP3A4 inducers (e.g., efavirenz, phenobarbital), or potent CYP3A4 inducers (e.g., carbamazepine, phenytoin, St John’s Wort) that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period (note: a list of prohibited concomitant medications and excluded and allowed CYP3A4 inhibitors and inducers is provided in Appendix D); b) or a renin inhibitor or more than one of an angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or angiotensin-receptor-neprilysin-inhibitor (ARNI); c) or a potassium-sparing diuretic that cannot be stopped prior to randomization and for the duration of the treatment period.
- Known hypersensitivity to the IP (active substance or excipients)
- Any other condition or therapy (e.g., breastfeeding, cardiogenic shock, clinically overt severe hepatic insufficiency [Child Pugh C], Addison’s disease, malignancy or other severe condition as per investigator’s judgment such as disease with <1 year life expectancy) which would make the participant unsuitable for this study and not allow participation for the full planned study period
- Concurrent or previous participation in another interventional clinical study using an investigational agent (e.g., not approved for any indication) within 30 days or 5 half-lives of the study drug, whichever is longer, prior to randomization.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Croatia | Recruiting | 01 Jun 2025 | 110 |
 Czechia | Not Yet Recruiting | 01 Jun 2025 | 100 |
 Greece | Recruiting | 01 Jun 2025 | 75 |
 Hungary | Recruiting | 01 Jun 2025 | 130 |
 Italy | Recruiting | 01 Jun 2025 | 70 |
 Poland | Recruiting | 01 Jun 2025 | 196 |
 Spain | Recruiting | 01 Jun 2025 | 135 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BAY 94-8862 | Test | FILM-COATED TABLET | ORAL | 20 | 42 | PRD1624191 |
Finerenone | Test | FILM COATED TABLET | ORAL | 10 | 42 | PRD9408175 |
Finerenone | Test | FILM COATED TABLET | ORAL | 40 | 42 | PRD9408174 |
Placebo for bay 94-8862 | Placebo | N/A | — | — | — | N/A |