| Eligibility |
Inclusion Criteria:
1. Adult male and female subjects (non-childbearing potential for females) ages 35
through 80 years at the time of screening who are capable of providing informed
consent prior to screening and any protocol-related procedures.
2. Written informed consent and any locally required authorization (e.g., Health
Insurance Portability and Accountability Act (HIPAA) in the USA) obtained from the
subject prior to performing any protocol-related procedures, including screening
evaluations.
3. Ability to complete and meet all eligibility requirements for randomization within 28
days of informed consent (56 days if washing out from lipid altering agent other than
statins or ezetimibe).
4. A diagnosis of stable atherosclerotic cardiovascular disease (CVD) documented prior to
screening:
- Coronary artery disease defined as a history of prior myocardial infarction,
coronary revascularization, history of coronary atherosclerosis based on invasive
or non-invasive imaging, and/or abnormal stress testing diagnostic of coronary
artery disease.
- Carotid artery disease (extracranial internal carotid artery (ICA) stenosis)
defined as evidence of carotid atherosclerosis by carotid imaging, or history of
percutaneous or surgical carotid revascularization
- Peripheral artery disease defined as ankle-brachial index < 0.90 and
claudication, or prior peripheral revascularization for ischemia, or evidence of
lower extremity (below the inguinal ligament) atherosclerosis on invasive or
noninvasive imaging
5. Currently receiving statin as standard of care, at a stable dose for = 8 weeks prior
to screening and intended to remain at a stable dose throughout the study duration.
Subjects may also be receiving ezetimibe, 10 mg/day for = 8 weeks prior to screening.
6. Nonsterilized males who are sexually active with a female partner of childbearing
potential must use condom and spermicide from Day 1 through the end of their
participation in the study. Because male condom and spermicide is not a highly
effective contraception method it is strongly recommended that female partners of a
male study subjects also use a highly effective method of contraception throughout
this period.
Exclusion Criteria:
1. Unstable cardiovascular conditions within 3 months prior to screening, including acute
coronary syndrome (ACS), stroke or transient ischemia attack, critical limb ischemia,
non-elective arterial revascularization, life-threatening arrhythmias, or heart
failure hospitalization.
2. Elective arterial revascularization (in any vascular territory) in the past 1 month.
Any planned arterial revascularization (coronary, peripheral or carotid).
3. New York Heart Association (NYHA) Class III or IV congestive heart failure or
treatment with advanced therapies (cardiac transplant, ventricular assist device,
cardiac resynchronization therapy,and/or chronic IV inotropic support), or severe
valvular heart disease.
4. Body mass index < 18 or > 45.
5. Lipid measurements with any of the following:
1. Triglycerides (TG) > 400 mg/dL
2. LDL-C > 120 mg/dL
3. High-density lipoprotein C (HDL-C) > 70 mg/dL for males or > 80 mg/dL for
females.
6. Clinically significant vital sign abnormalities at screening or on Day -1:
1. Systolic blood pressure (BP) < 90 or >160 mm Hg
2. Diastolic BP > 100 mm Hg
7. Females currently breastfeeding or of childbearing potential. Females of childbearing
potential are defined as those who are not surgically sterile (i.e., bilateral tubal
ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not
postmenopausal; defined as 12 months with no menses without an alternative medical
cause and a follicle-stimulating hormone level in the central laboratory's normal
range for post-menopausal phase is required at screening.
8. Use of lipid-lowering medications, with the exception of statins and ezetimibe, and
the following dietary supplements: = 2 grams/day of fish oil (= 2 grams/day
docosahexaenoic acid (DHA) and EPA combined), = 30 grams/day of flaxseed oil or ground
flaxseed, red yeast extract, > 100 mg/day of niacin. At the investigator's discretion,
subjects may undergo a 6-week washout period of any exclusionary lipid-lowering agents
with the expectation that post-washout lipid levels will be rechecked and acceptable
per above criteria.
9. History of any of the following:
- Documented familial hypercholesterolemia
- Chronic kidney disease defined by estimated glomerular filtration rate < 30
mL/min/1.73 m2 by the modification of diet in renal disease equation, or end
stage renal disease treated with kidney transplant or renal replacement therapy
- History of clinically overt chronic liver disease or biochemical evidence of
liver disease
- Poorly controlled endocrine disorder including:
- Type 1 Diabetes excluded
- Type 2 Diabetes Mellitus with glycated hemoglobin (HbA1c) > 8.0% as assessed
at screening or
- Uncontrolled thyroid disorder defined as thyroid stimulating hormone (TSH)> upper
limit of normal (ULN) and abnormal free T4; subjects with thyroid deficiency
should have received a stable dose of thyroid hormone for > 6 weeks prior to
screening and have a normal TSH.
- Current or previous use of systemic corticosteroids within 28 days prior to
screening. Topical, intra-articular, intranasal, inhaled, and ophthalmic steroid
therapies are allowed
- History of severe infection or ongoing febrile illness within 30 days of
screening, or a medical history of a chronic viral illness including hepatitis B
or C virus, or human immunodeficiency virus (HIV).
- History of active malignancy within 5 years (subjects with non-melanotic skin
cancer may be included)
- Any other disease or condition or laboratory value that, in the opinion of the
investigator or medical monitor, would place the subject at an unacceptable risk
or interfere with the evaluation of the investigative product.
- Known allergy/hypersensitivity to any component of the investigational product
formulation, other biologics, IV infusion equipment, plastics, adhesive or
silicone, history of infusion site reactions with IV administration of other
medicines, or ongoing clinically important allergy/hypersensitivity as judged by
the investigator.
10. Subjects who are legally institutionalized
11. Previous Exposure to rhLCAT
12. Concurrent enrollment in another clinical study of any investigational drug therapy or
use of any biologicals within 6 months prior to screening or within 5 half-lives of an
investigational agent or biologic, whichever is longer.
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