Clinical Trial Page

Summary
EudraCT Number:2020-000306-29
Sponsor's Protocol Code Number:20103
National Competent Authority:Greece - EOF
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2020-06-03
Trial results
A. Protocol Information
A.1Member State ConcernedGreece - EOF
A.2EudraCT number2020-000306-29
A.3Full title of the trial
A multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of finerenone on morbidity and mortality in participants with heart failure (NYHA II-IV) and left ventricular ejection fraction ≥ 40% (LVEF ≥ 40%).
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure.
A.3.2Name or abbreviated title of the trial where available
FINEARTS-HF
A.4.1Sponsor's protocol code number20103
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorBayer AG
B.1.3.4CountryGermany
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportBayer AG
B.4.2CountryGermany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationBayer AG
B.5.2Functional name of contact pointBayer Clinical Trials Contact
B.5.3 Address:
B.5.3.1Street AddressN/A
B.5.3.2Town/ cityBerlin
B.5.3.3Post code13342
B.5.3.4CountryGermany
B.5.4Telephone number004962115045150
B.5.6E-mailclinical-trials-contact@bayer.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFinerenone
D.3.2Product code BAY 94-8862 IR tablet 10 mg
D.3.4Pharmaceutical form Coated tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFINERENONE
D.3.9.1CAS number 1050477-31-0
D.3.9.2Current sponsor codeBAY 94-8862
D.3.9.4EV Substance CodeSUB183743
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFinerenone
D.3.2Product code BAY 94-8862 IR tablet 20 mg
D.3.4Pharmaceutical form Coated tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFINERENONE
D.3.9.1CAS number 1050477-31-0
D.3.9.2Current sponsor codeBAY 94-8862
D.3.9.4EV Substance CodeSUB183743
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number20
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFinerenone
D.3.2Product code BAY 94-8862 IR tablet 40 mg
D.3.4Pharmaceutical form Coated tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFINERENONE
D.3.9.1CAS number 1050477-31-0
D.3.9.2Current sponsor codeBAY 94-8862
D.3.9.4EV Substance CodeSUB183743
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number40
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboCoated tablet
D.8.4Route of administration of the placeboOral use
D.8 Placebo: 2
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboCoated tablet
D.8.4Route of administration of the placeboOral use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Heart failure
E.1.1.1Medical condition in easily understood language
Medical condition in which the heart is not pumping as well as it should be.
E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10019279
E.1.2Term Heart failure
E.1.2System Organ Class 10007541 - Cardiac disorders
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To demonstrate the superiority of finerenone to placebo in reducing the rate of the composite CV endpoint.
E.2.2Secondary objectives of the trial
1. To determine superiority of finerenone to placebo for each secondary endpoint.
2. To assess the safety and tolerability of finerenone.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Participant (male or female) must be aged 40 years and older, at the time of signing the informed consent.
2. Diagnosis of heart failure with NYHA class II–IV, ambulatory or hospitalized primarily for heart failure.
3. On diuretic treatment for at least 30 days prior to randomization
4. Documented LVEF of ≥40% measured by any modality within the last 12 months.
5. Structural heart abnormalities based on any local imaging measurement within the last 12 months, defined by at least one of the following findings: LAD ≥3.8cm, LAA ≥20cm2, LAVI >30 mL/m2, LVMI ≥115 g/m2 (male)/ 95 g/m2 (female), septal thickness or posterior wall thickness ≥1.1 cm
6. n-terminal prohormone B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL (BNP ≥100 pg/mL) in sinus rhythm and patient does not have an ongoing diagnosis of paroxysmal atrial fibrillation or NT proBNP ≥900 pg/mL (BNP ≥300 pg/mL) in atrial fibrillation (or if atrial fibrillation status is unknown or if patient has an ongoing diagnosis of paroxysmal atrial fibrillation) for participants obtained at the following time:
- Within 90 days prior to randomization if patient had been hospitalized for HF requiring initiation or change in HF therapy or if patient had an urgent visit for HF requiring intravenous (IV) diuretic therapy, both within 90 days prior to randomization
OR
- Within 30 days prior to randomization if patient has not been hospitalized for HF nor had an urgent HF visit within the past 90 days.
7. Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and baseline and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for those participating in clinical trials.
8. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
E.4Principal exclusion criteria
1. Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m² at either screening or randomization visit
2. Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit
3. Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to randomization
4. Myocardial infarction or any event which could have reduced the ejection fraction within 90 days prior to randomization
5. Coronary artery bypass graft surgery in the 90 days prior to randomization
6. Percutaneous coronary intervention in the 30 days prior to randomization
7. Stroke or transient ischemic cerebral attack within 90 days prior to randomization
8. Probable alternative cause of participants’ HF symptoms that in the opinion of the investigator primarily accounts for patient’s dyspnea such as significant pulmonary disease, anemia or obesity. Specifically, patients with the below are excluded:
- Severe pulmonary disease requiring home oxygen, or chronic oral steroid therapy
- History of primary pulmonary arterial hypertension
- Hemoglobin <10 g/dl*
- Valvular heart disease considered by the investigator to be clinically significant
- BMI >50 kg/m2 at screening
9. SBP ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at least 2-minute apart, at screening or at randomization
10. Life-threatening or uncontrolled arrhythmias at screening and/or randomization including but not limited to sustained ventricular tachycardia and atrial fibrillation, or atrial flutter with resting ventricular rate >110 bpm
11. Symptomatic hypotension with mean systolic blood pressure <90 mmHg at screening or at randomization
12. Any primary cause of HF scheduled for surgery, e.g. valve disease such as severe aortic stenosis or severe mitral regurgitation by the time of screening or randomization
13. History of peripartum cardiomyopathy, chemotherapy induced cardiomyopathy, viral myocarditis, right heart failure in absence of left-sided structural disease, pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative
cardiomyopathy including amyloidosis
14. Presence of left ventricular assist device by the time of screening or randomization
15. History of hyperkalemia or acute renal failure during MRA treatment for >7 consecutive days, leading to permanent discontinuation of the MRA treatment
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin urine or serum test
17. Known hypersensitivity to the study intervention (active substance or excipients)
18. Hepatic insufficiency classified as Child-Pugh C at screening or randomization
19. Addison’s disease
20. Requirement of any IV vasodilating drug (e.g. nitrates, nitroprusside), any IV natriuretic peptide (e.g. nesiritide, carperitide), any IV positive inotropic agents, or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) within 24 hours prior to randomization
21. Participants who require treatment with more than one ACEI, ARB or angiotensin-receptor neprilysin inhibitor (ARNI), or two simultaneously at randomization
22. Continuous (at least 90 days) treatment with an MRA (e.g. spironolactone, eplerenone, canrenone, esaxerenone) within 12 months prior to screening. Last intake at least 30 days before randomization. Treatment with MRA should not be interrupted with the purpose of enrollment into the study
23. Concomitant treatment with any renin inhibitor or potassium-sparing diuretic that cannot be stopped prior to randomization and for the duration of the treatment period
24. Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin) or moderate or potent CYP3A4 inducers, that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period

*Assessment of relevant laboratory parameters is only required if there is a clinical suspicion of anemia (as an alternative cause of HF symptoms) or hepatic insufficiency.
E.5 End points
E.5.1Primary end point(s)
Composite of Cardiovascular (CV) death and total (first and recurrent) HF events (HHF or urgent HF visit) in HF patients (New York Heart Association [NYHA] class II–IV) and LVEF ≥40%.
E.5.1.1Timepoint(s) of evaluation of this end point
Up to end of study (i.e. up to 42 months)
E.5.2Secondary end point(s)
1. Time to total (first and recurrent) HF events
2. Improvement in NYHA class from Baseline to Month 12
3. Change from baseline to Month 6, 9 and 12 in Total Symptom Score (TSS) from Kansas City Cardiomyopathy Questionnaire (KCCQ)
4. Time to first occurrence of composite renal endpoint: sustained decrease in eGFR ≥50% relative to baseline over at least 4 weeks, or sustained eGFR decline to <15ml/min/1.73m2 or initiation of dialysis or renal transplantation
5. Time to all-cause mortality
E.5.2.1Timepoint(s) of evaluation of this end point
1. Up to end of study (i.e. up to 42 months)
2. Up to 12 month after start of treatment
3. Up to 12 month after start of treatment
4. Up to end of study (i.e. up to 42 months)
5. Up to end of study (i.e. up to 42 months)
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Biomarkers and Quality of Life
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned12
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA346
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Argentina
Colombia
Malaysia
New Zealand
Ukraine
Hong Kong
Taiwan
Australia
Brazil
Canada
China
India
Israel
Japan
Korea, Republic of
Mexico
Russian Federation
United Kingdom
United States
Austria
Bulgaria
Czechia
Denmark
Finland
Germany
Greece
Hungary
Italy
Latvia
Lithuania
Netherlands
Poland
Portugal
Romania
Slovakia
Spain
Türkiye
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Last Patient Last Visit
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months11
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 1500
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 4000
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state240
F.4.2 For a multinational trial
F.4.2.1In the EEA 3637
F.4.2.2In the whole clinical trial 5500
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2020-07-13
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2020-07-01
P. End of Trial
P.End of Trial StatusOngoing
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