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 DiseaseTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]MedDRA version: 14.1Level: LLTClassification code 10011079Term: Coronary artery disease NOSSystem Organ Class: 100000004849
- Registration Number
- EUCTR2012-004208-37-GR
- 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.
- 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 (1.55-2.07mmol/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 (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 ankle-brachial index equal to or
less than 0.9 in either leg at rest.
• History of intermittent claudication (WHO criteria as above)
TOGETHER WITH either previous intervention by
amputation, or reconstructive vascular surgery, or
angioplasty in one or both legs because of atherosclerotic
disease within the last 2 years.
- Documented abdominal aortic aneurysm,
• AAA is considered to be present when the min
- 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.
- CK > 3 times the ULN at screening or at end of lipid stabilization period
- 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 postmenopausal range for the laboratory involved) in a female < 55 years old unless the subj
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