Chronic Heart Failure With Reduced Ejection Fraction MedDRA version: 20.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: Omecamtiv mecarbil
Product Code: AMG 423
Pharmaceutical Form: Modified-release tablet
INN or Proposed INN: Omecamtiv Mecarbil
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject has provided informed consent Male or female, = 18 to = 85 years of age at signing of informed consent History of chronic HF (defined as requiring treatment for HF for a minimum of 30 days before randomization) LVEF = 35%, per subject's most recent medical record, within 12 months prior to screening. The most recent qualifying LVEF must be at least 30 days after any of the following, if applicable: 1) an event likely to decrease EF (eg, myocardial infarction, sepsis); 2) an intervention likely to increase EF (eg, cardiac resynchronization therapy, coronary revascularization); or 3) the first ever presentation for HF. NYHA class II to IV at most recent screening assessment Managed with HF SoC therapies consistent with regional clinical practice guidelines according to investigator judgment of subject's clinical status Oral SoC therapies for chronic HF (eg, beta blockers, renin-angiotensinaldosterone system inhibitors) should be present, if not contraindicated. Subjects enrolled during either HF hospitalization or early after HF hospitalization discharge can be reinitiating or titrating oral SoC chronic HF therapies at the same time of randomization with the goal of achieving optimized therapy on study. Currently hospitalized with primary reason of HF OR one of the following events within 1 year to screening: 1) hospitalization with primary reason of HF; 2) urgent visit to ED with primary reason of HF B-type natriuretic peptide (BNP) level = 125 pg/mL or an NT-proBNP level = 400 pg/mL at most recent screening assessment (subjects receiving angiotensin receptor-neprilysin inhibitor [ARNi] must use NT-proBNP assessment; for subjects in atrial fibrillation/flutter at screening, the cut off levels are: BNP = 375 pg/mL or NT-proBNP = 1200 pg/mL) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7457 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 828
Exclusion criteria
Exclusion criteria: Factors expected to interfere with the subject's availability or ability to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge (including ongoing substance abuse). Inability to swallow study medication tablet (eg, swallowing disorders, feeding tubes) Receiving mechanical hemodynamic support (eg, intra-aortic balloon pump counterpulsation), or invasive mechanical ventilation = 7 days prior to randomization Receiving IV inotropes (eg, dobutamine, milrinone, levosimendan) or IV vasopressors (eg, epinephrine, norepinephrine, dopamine, or vasopressin) = 3 days prior to randomization Receiving IV diuretics or IV vasodilators, supplemental oxygen therapy, or non-invasive mechanical ventilation (eg, bilevel positive airway pressure [BiPAP] or continuous positive airway pressure [CPAP] = 12 hours prior to randomization (Note: the use of non-invasive ventilation for sleep disordered breathing is permitted) Acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina), stroke, or transient ischemic attack, major cardiac surgery or cardiac intervention (ie, implantation of cardiac closure devices, cardiac resynchronization therapy, or catheter ablation), percutaneous coronary intervention, or valvuloplasty/other cardiac valve repair or implantation within the 3 months prior to randomization Insertion of other cardiac devices (eg, implantable cardioverter defibrillator, permanent pacemaker, monitoring devices) within 30 days prior to randomization Severe uncorrected valvular heart disease, hypertrophic or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Composite of time to CV death or first HF event, whichever occurs first.;Timepoint(s) of evaluation of this end point: Duration of trial; Main Objective: To evaluate the effect of treatment with omecamtiv mecarbil compared with placebo on the time to cardiovascular (CV) death or first HF event, whichever occurs first, in subjects with chronic HF with reduced ejection fraction (HFrEF) receiving standard of care (SoC) therapy. An HF event is defined as presentation of the patient for an urgent, unscheduled clinic/office/ED visit, or hospital admission, with a primary diagnosis of HF, where the patient exhibits new or worsening symptoms of HF on presentation, has objective evidence of new or worsening HF, and receives initiation or intensification of treatment specifically for HF (Hicks et al, 2015). Changes to oral diuretic therapy do not qualify as initiation or intensification of treatment. ; Secondary Objective: To evaluate the effects of OM on time to: - CV death - HF hospitalization - all-cause death To evaluate the effects of treatment with OM on change in patient-reported outcomes (PROs). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to CV death. Change in Kansas City Cardiomyopathy Questionnaire Total Symptoms Score (KCCQ TSS) from baseline to Week 24. Time to first HF hospitalization. Time to all-cause death. ;Timepoint(s) of evaluation of this end point: Duration of trial | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed