A study to look at the effect of AMG 145 on the build up of a waxy substance (plaque) in the arteries of the heart, using a method to see inside the heart.
- Conditions
- Coronary Artery DiseaseMedDRA version: 16.0Level: LLTClassification code 10011079Term: Coronary artery disease NOSSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2012-004208-37-ES
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 950
- Subject has provided informed consent
- Male or female ? 18 age at screening
- Clinical indication for coronary angiography
- Subjects must meet all of the following IVUS criteria at the qualifying coronary catheterization procedure:
A. Entire Coronary Circulation:
- Angiographic evidence of coronary heart disease as defined by at least one lesion in any of the three major native coronary arteries that has >20% reduction in lumen diameter by angiographic visual estimation or prior history of PCI.
- This vessel need not be the target coronary artery for IVUS.
- Any vessel with previous PCI may not be used as the target coronary artery.
B. Left Main Coronary Artery:
- Must not have a > 50% reduction in lumen diameter by visual angiographic estimation.
C. Target Coronary Artery for IVUS
- Must be accessible to the IVUS catheter.
- Must not have a >50% reduction in lumen diameter by angiographic
visual estimation within the target segment, the target segment being at
least 40 mm in length.
- A lesion, distal to the target segment, of up to 60% stenosis is
permitted, provided that the stenosis is not a target for PCI or CABG.
- A single branch of the target vessel may have a narrowing of <70%
by visual estimation, provided that the branch in question is not a target
for PCI or CABG.
- Must have a <50% reduction in lumen diameter by angiographic visual estimation throughout a segment of at least 40 mm in length (the ?target segment?). A lesion of up to 60% stenosis is permitted, distal to the target segment. A single branch of the ?target vessel? may have a narrowing up to but <70% by visual estimation, as long as the target segment contains no lesion >50%, provided that the branch in question is not a target for PCI or CABG.
- Has not undergone prior percutaneous coronary intervention or coronary artery bypass graft surgery.
- The target vessel is not currently a candidate for intervention or a likely candidate for intervention over the next 18 months.
- The target vessel may not be a bypass graft.
- The target vessel may not be a bypassed vessel.
- The target vessel may not be the culprit vessel for a previous MI.
- Subjects already taking a statin at the time of the initial screening LDL-C assessment must be on a stable dose of statin therapy for at least 4 weeks prior to the initial screening LDL-C assessment.
- Fasting LDL-C as determined by local laboratory both at the initial screening visit (a local LDL-C level may be used for the initial screening LDL-C level as long as it was drawn within 4 weeks of screening visit) and if applicable at the end of the lipid stabilization period :
LDL-C ? 80 mg/dL (2.07 mmol/L)
OR
LDL-C ? 60 -80 mg/dL (1.55-2.07 mmol/L) in the presence of one Major or three Minor Risk factors. Enrollment of subjects with LDL-C between ? 60 mg/dL (1.55 mmol/L) and < 80 mg/dL (2.07 mmol/L) will be limited to no more than approximately 25% of total planned enrollment.
Major Risk Factors (one required)
1) Non-coronary atherosclerotic vascular disease as evidenced by one of the following documented peripheral arterial disease (PAD),
documented abdominal aortic aneurysm (AAA), or documented
cerebrovascular disease (CD).
- Documented peripheral arterial disease (PAD- one of the
following primary criteria must be satisfied):
? Current intermittent claudication (WHO criteria, e.g., leg
pain occurring only while walking and disappearing in less
than 10 minutes on standing) of presumed atherosclerotic
origin TOGETHER WITH
- Clinically significant heart disease which in the opinion of the Principal Investigator is likely to require coronary bypass surgery, PCI, cardiac transplantation, surgical valve repair and/or replacement during the course of the study.
- Coronary artery bypass surgery <6 weeks prior to the qualifying IVUS.
- NYHA III or IV heart failure, or last known left ventricular ejection fraction < 30%
- Uncontrolled cardiac arrhythmia defined as recurrent and highly
symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to randomization
- Known hemorrhagic stroke
- Uncontrolled hypertension at Randomization visit, defined as a resting systolic blood pressure of ? 180mmHg.
- Personal or family history of hereditary muscular disorders
- Fasting triglycerides ? 400 mg/dL (4.5 mmol/L) at screening and at end of lipid stabilization period
- Subject has taken a cholesterol ester transfer protein (CETP) inhibitor in the last 12 months prior to LDL-C screening, such as: anacetrapib, dalcetrapib or evacetrapib.
- Type 1 diabetes or poorly controlled type 2 diabetes (HbA1c > 9%) at screening.
- Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (eg IV, intramuscular [IM], or PO) ) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted)
- Hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone TSH below the lower limit of normal (LLN) or > 1.5 times the upper limit of normal (ULN), respectively, at screening
- Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening, confirmed by a repeat measurement at least 1 week apart
- Active liver disease or hepatic dysfunction, defined as aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as determined by analysis at screening or at end of lipid stabilization period, confirmed by a repeat measurement at least 1 week apart
- CK > 3 times the ULN at screening or at end of lipid stabilization period, confirmed by a repeat measurement at least 1 week apart
- Known active infection or major hematologic, renal, metabolic,
gastrointestinal or endocrine dysfunction in the judgment of the
investigator
- Baseline IVUS does not meet IVUS Core Lab technical standards
- Unreliability as a study participant based on the investigator's (or
designee?s) knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
- Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
- Female subject who is not willing to use at least 1 highly effective method of birth control during treatment and for an additional 15 weeks after the end of treatment unless subject is sterilized or postmenopausal;
? Menopause is defined as 12 months of spontaneous and continuous amenorrhea in a female ? 55 years old or 12 months of spontaneous and continuous amenorrhea with a follicle-stimulating hormone (FSH) level > 40 IU/L (or according to the definition of postm
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of AMG 145 on the change in burden of coronary atherosclerosis as measured by percent atheroma volume (PAV) in patients with coronary artery disease requiring angiography for a clinical indication who are taking atorvastatin.;Secondary Objective: To evaluate the effect of AMG 145 on the change in normalized total atheroma volume (TAV) and the percentage of patients who demonstrate regression of coronary atherosclerosis.;Primary end point(s): The nominal change in percent atheroma volume (PAV) from baseline to 78 weeks post randomization;Timepoint(s) of evaluation of this end point: Baseline and week 78
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Percentage of subjects demonstrating regression (any reduction from baseline) in PAV<br>- Nominal change in normalized TAV from baseline to 78 weeks<br>- Percentage of subjects demonstrating regression (any reduction from baseline) in TAV;Timepoint(s) of evaluation of this end point: Baseline and week 78