A Study to Test Whether BI 690517 in Combination With Empagliflozin Helps People With Heart Failure

Heart Failure Clinical Trial

Official title:

EASi-HF - A Phase III Double-blind, Randomised, Parallel-group Superiority Trial to Evaluate Efficacy and Safety of the Combined Use of Oral BI 690517 and Empagliflozin Compared With Placebo and Empagliflozin in Participants With Symptomatic Heart Failure (HF: NYHA II-IV) and Left Ventricular Ejection Fraction (LVEF) ≥40%

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06424288
• Other study ID #: 1378-0020
• Secondary ID: 2023-509706-30-0
• Status: Recruiting
• Phase: Phase 3
• Start date: June 4, 2024
• Est. completion date: November 15, 2027

Study information

• Verified date: June 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: lintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is open to adults aged 18 or above legal age with heart failure. People can join the study if they have heart failure symptoms and a left ventricular ejection fraction (LVEF) of 40% or more. The purpose of this study is to find out whether BI 690517 in combination with empagliflozin helps people with heart failure.

Participants are put into 2 groups by chance. Every participant has an equal chance of being in each group. The groups are:

• BI 690517 and empagliflozin group: participants take BI 690517 and empagliflozin as tablets once a day.

• Placebo and empagliflozin group: participants take placebo and empagliflozin as tablets once a day.

Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, they visit their doctors regularly. The doctors regularly check participants' health and take note of any unwanted effects. The study staff may also contact the participants by phone. Participants also regularly answer questions about their well-being.

The study does not have a fixed duration. It continues until we have enough data to see if the treatment is working.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6000
• Est. completion date: November 15, 2027
• Est. primary completion date: November 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years

2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial

3. Male or female participants. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information

4. Chronic Heart failure (HF) diagnosed at least 3 months before Visit 1, and in New York Heart Association (NYHA) class II-IV at Visit 1, with left ventricular ejection fraction (LVEF) =40% per local reading. A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before Visit 2

5. Presence of structural heart abnormality (confirmed by any imaging modality; i.e. echocardiography at Visit 1, as defined by left ventricular hypertrophy or left atrial enlargement). Historical imaging may be used if performed within 12 months prior to Visit 1, or imaging may be completed after study consent has been obtained and before Visit 2

6. Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysed at the central laboratory at Visit 1:

1. in participants with body mass index (BMI) <27 kg/m²: =300 pg/mL for participants without atrial fibrillation (Afib) or atrial flutter (Aflutter) (at Visit 1 electrocardiogram (ECG)) and =900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)

2. in participants with BMI =27 kg/m² to <35 kg/m²: =220 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and =660 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)

3. in participants with BMI =35 kg/m²: =125 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and =375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)

7. At least one of the following:

• Currently treated with diuretic therapy e.g. loop diuretics or thiazides, and on a stable dose for at least 1 week prior to Visit 1

• Documented hospitalisation for HF within 6 months prior to Visit 1

• Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1

• in participants without Afib or Aflutter (at Visit 1 ECG): =900 pg/mL

• for participants with Afib or Aflutter (at Visit 1 ECG): =1800 pg/mL

8. Participants must be treated according to best possible standard of care (SOC) in accordance with applicable HF local/international guidelines (according to the judgment of the investigator)

Exclusion criteria:

1. Treatment with an mineralocorticoid receptor antagonist (MRA) (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator. Treatment with MRA should not be interrupted with the intention of enrolment into the study

2. Treatment with amiloride, or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator

3. Receiving the following treatments:

• a direct renin inhibitor (e.g. aliskiren) at Visit 2

• more than one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI), or two simultaneously at Visit 2

• Acute decompensated HF requiring hospitalisation or i.v. therapy including diuretics, or i.v. inotropes or i.v. vasodilators, mechanical support (such as an intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device), or IV natriuretic peptide (e.g. nesiritide) within the past 7 days prior to Visit 2

4. Myocardial infarction (MI), cerebrovascular accident (CVA), transient ischemic attack (TIA), stroke, coronary artery bypass graft (CABG) surgery, heart valve surgery or any other major surgery (major according to the investigator's assessment) within 90 days prior to Visit 1, or scheduled for major elective surgery (e.g. hip replacement, coronary artery bypass graft surgery/CABG)

5. Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device (LVAD)

6. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to Visit 1 and until Visit 2

7. Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1 and until Visit 2

8. Known severe valvular heart disease (obstructive or regurgitant), as per investigator's judgment, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study Further exclusion criteria apply.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• BI 690517
BI 690517
• Empagliflozin
Empagliflozin
• Placebo
Placebo matching BI 690517

Locations

Country	Name	City	State
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first event of Cardiovascular (CV) death or Hospitalisation for heart failure (HHF)		up to 42 months
Secondary	Key secondary endpoint: Time to first event of CV death, HHF or urgent heart failure visit		up to 42 months
Secondary	Key secondary endpoint: Occurrence of HHFs (first and recurrent)		up to 42 months
Secondary	Key secondary endpoint: Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) at Week 32	The Kansas City Cardiomyopathy Questionnaire is a patient-reported outcome instrument for use in clinical investigations in heart failure.; The Total Symptom Score measures the following aspects of symptom experience in two domain scores: The "Symptom Frequency Domain" assesses frequency of the following experiences: Lower extremity swelling in the morning; Fatigue limiting patients' ability to do what they want; Dyspnea limiting patients' ability to do what they want; Dyspnea forcing patients to sleep upright/elevated; The "Symptom Burden Domain" assesses bothersomeness of the following symptoms: Fatigue; Dyspnea; Lower extremity swelling All KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.	at baseline, at week 32
Secondary	Key secondary endpoint: Time to CV death		up to 42 months
Secondary	Key secondary endpoint: Time to all-cause mortality		up to 42 months
Secondary	Time to first HHF		up to 42 months
Secondary	Time to first occurrence of death from kidney failure, chronic dialysis* or renal transplant or sustained reduction of =40% estimated glomerular filtration rate (eGFR)** or sustained eGFR (CKD-EPI)cr <10 mL/min/1.73 m² (composite renal endpoint)	* chronic dialysis is defined as dialysis continuing for at least 30 days; ** using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation ((CKD-EPI)cr)	up to 42 months
Secondary	Absolute change from baseline in KCCQ Clinical Summary Score (KCCQ-CSS) at Week 32	The KCCQ Clinical Summary Score is a composite of the Total Symptom Score and Physical Limitations Score.; The "Physical Limitations Score" measures the following physical limitations: Dressing; Showering/bathing; Walking one block on level ground; Doing yardwork, housework or carrying groceries; Climbing a flight of stairs without stopping; Hurrying or jogging as if to catch a bus All KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.	at baseline, at week 32
Secondary	Absolute change from baseline in KCCQ-TSS at Week 52		at baseline, at week 52

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