Principal Investigator: James Fang
Keywords: Heart failure , HFrEF Department: Cardiovascular Medicine
IRB Number: 00103398
Specialty: Cardiology, Cardiology
Sub Specialties: Heart Failure
Recruitment Status: Recruiting

Contact Information

Jonathan Gutierrez
Jonathan.Gutierrez@utah.edu
801-587-4877

Brief Summary

Primary Objective:

• to evaluate the effect of treatment with omecamtiv mecarbil (OM) 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 Changes to oral diuretic therapy do not qualify as

initiation or intensification of treatment.

 

Secondary Objectives:

• 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)

 

Safety Objective:

• to evaluate the safety of OM as measured by subject incidence of reported adverse events,

including serious adverse events of ventricular arrhythmias requiring treatment and positively

adjudicated major cardiac ischemic events (fatal and nonfatal myocardial infarction, unstable

angina hospitalization, and coronary revascularization)

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-angiotensin-aldosterone 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 with atrial fibrillation, the cut off levels are:
BNP ≥ 375 pg/mL or NT-proBNP ≥ 1200 pg/mL)
 

Exclusion Criteria

Currently receiving treatment in another investigational device or drug study, or
< 30 days since ending treatment on another investigational device or drug
study(ies). Other investigational procedures while participating in this study are
excluded.

Malignancy within 5 years prior to randomization with the following exceptions:
localized basal or squamous cell carcinoma of the skin, cervical intraepithelial
neoplasia, stage 1 prostate carcinoma, breast ductal carcinoma in situ.

Subject has known sensitivity to any of the products or components to be
administered during dosing.

Subject not likely to be available 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.

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, or supplemental oxygen therapy
≤ 12 hours prior to randomization

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

Implantable cardioverter defibrillator or initiation of cardiac resynchronization
therapy (CRT) (with/without implantable cardioverter defibrillator) 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

Untreated severe ventricular arrhythmia (eg, ventricular tachycardia or ventricular
fibrillation)

Chronic antiarrhythmic therapy, with the exception of amiodarone. Note: for the
purposes of this exclusion criterion, digoxin, calcium channel blocker, and
beta-blocker therapy are not considered to be chronic antiarrhythmic therapies

Symptomatic bradycardia or second or third degree heart block without a
pacemaker

Routinely scheduled outpatient intravenous infusions for HF (eg, inotropes,
vasodilators [eg, nesiritide], diuretics) or routinely scheduled ultrafiltration

Systolic blood pressure > 140 mmHg or < 85 mmHg, or diastolic blood pressure
> 90 mmHg, or heart rate > 110 beats per minute, or < 50 beats per minute at
screening

Estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 or receiving
dialysis at screening

Hepatic impairment defined by a total bilirubin (TBL) ≥ 2 times the upper limit of
normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) ≥ 3 times ULN at screening

Previously received OM

Severe, concomitant non-CV disease that is expected to reduce life expectancy
to < 2 years

Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow,
renal) or anticipated to receive chronic mechanical circulatory support or
heart transplantation within 12 months from randomization

Female subject of childbearing potential who is not willing to inform her partner of
her participation in this clinical study and to use 2 acceptable methods of
effective birth control or practice true sexual abstinence (the reliability of sexual
abstinence must be evaluated by the investigator and be the preferred and usual
lifestyle of the subject) during treatment with IP (OM or placebo) and for an
additional 5 days after the last dose of IP. If the female subject or her sole male
partner has had a surgical contraceptive method (bilateral tubal ligation/occlusion
or vasectomy with medical assessment of surgical success), additional
contraceptive methods are not required. Male subject with a female partner of
childbearing potential and not willing to inform his partner of his participation in
this clinical study.


• A female is considered of childbearing potential unless she has had a
hysterectomy, bilateral oophorectomy, or bilateral salpingectomy or she is
postmenopausal. Menopause is defined as ≥ 12 months of spontaneous and
continuous amenorrhea in a female ≥ 55 years old; or no spontaneous
menses for at least 2 years in a female < 55 years old; or age < 55 years and
spontaneous menses within the past 1 year, but currently amenorrheic (eg,
spontaneous or secondary to hysterectomy) and with follicle-stimulating
hormone (FSH) levels > 40 IU/L, or postmenopausal estradiol levels
(< 5 ng/dL), or according to the definition of “postmenopausal range” for the
laboratory involved.

• Two acceptable methods of effective birth control include the following
2 options:
− use of hormonal and barrier combination birth control methods
(intrauterine device and barrier method with spermicide, intrauterine device
and hormonal birth control method, hormonal birth control method and barrier
method with spermicide),
− 2 barrier methods (each partner must use 1 barrier method except a
female condom) with at least 1 of the barrier methods including spermicide (a
male and female condom may not be used together due to the risk of tearing)

• Hormonal methods of birth control include oral, intravaginal, transdermal,
injectable, or implantable. Barrier methods of birth control include diaphragm
with spermicide, cervical cap with spermicide, male or female condom with
spermicide, and contraceptive sponge with spermicide. If spermicide is not
commercially available in the local country/region a barrier method without
spermicide is acceptable.
− Note: If additional medications are given during treatment which may
alter the contraceptive requirements (these additional medications may
require an increase in the number of contraceptive methods and/or length of
time that contraception is to be utilized after the last dose of protocol-required
therapies) the investigator is to discuss these changes with the study subject.

Female subject is pregnant or breastfeeding or is planning to become pregnant
or planning to breastfeed during treatment with IP (OM or placebo) or within
5 days after the end of treatment with IP.

Planned to be discharged from the hospital to long term care facility (eg, skilled
nursing facility) or hospice.

History or evidence of any other clinically significant disorder (including cardiac
arrhythmia), condition or disease (with the exception of those outlined above)
that, in the opinion of the investigator or Amgen physician, if consulted, would
pose a risk to subject safety or interfere with the study evaluation, procedures, or
completion.