A Randomized, Multi-center, Placebo-controlled, Parallel-group Study to Determine the Effects of AMG 145 Treatment on Atherosclerotic Disease Burden as Measured by Intravascular Ultrasound in Subjects Undergoing Coronary Catheterization

Trial ID:
IRB-14-6370
Paul Teirstein
This study will evaluate whether low-density lipoprotein (LDL-C) lowering with Evolocumab (AMG 145) results in greater change from baseline in per

Inclusion Criteria:

  • Male or Female ≥ 18 years of age
  • Clinical indication for coronary angiography
  • Subjects already taking statin therapy, niacin or ezetimibe at screening must have been on a stable dose for at least 4 weeks prior to screening LDL-C. Subjects not taking lipid-regulating therapy must enter the study via a lipid stabilization period. Subjects who are intolerant to statins must meet statin intolerance entry criteria
  • Fasting LDL-C ≥ 80 mg/dL (2.07 mmol/L) with or without additional risk factors, or, LDL-C ≥ 60 -<80 mg/dL (1.55-2.07 mmol/L) in the presence of one major or three minor risk factors as defined below.

Major Risk Factors (1 required):

  • 1. Non coronary atherosclerotic vascular disease (documented peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA) or cerebrovascular disease (CD)).
  • 2. Documented history of myocardial infarction or hospitalization for unstable angina within the last 2 years
  • 3. Documented Type 2 diabetes mellitus Minor Risk factors (three required): Current cigarette smoker, Hypertension, Low HDL cholesterol, Family history of premature CHD, age or hs-CRP ≥ 2 mg/dL

Subjects must meet the following criteria at the qualifying coronary catheterization procedure:

  • Evidence of coronary heart disease (at least one lesion in a native coronary artery that has >20% reduction in lumen diameter) or prior PCI
  • Left main coronary artery <50% reduction in lumen diameter by visual estimation
  • Target Coronary Artery for IVUS must be accessible to the IVUS catheter, must not have a >50% reduction in lumen diameter within the target segment (and at least 40mm in length); cannot have undergone prior PCI or CABG and is not a candidate for intervention over the next 18 months. It may not be a bypass graft, bypassed vessel or culprit vessel for previous MI.

Exclusion Criteria:

  • Clinically significant heart disease likely to require intervention during the course of the study
  • Coronary artery bypass graft surgery < 6 weeks prior to the qualifying IVUS
  • NYHA III or IV heart failure, or last known left ventricular ejection fraction less than 30%
  • Uncontrolled cardiac arrhythmia
  • Known hemorrhagic stroke
  • Uncontrolled hypertension at randomization
  • Personal or family history of hereditary muscular disorders
  • Fasting TGs ≥ 400 mg/dL (4.5 mmol/L) at screening
  • Subject has taken a CETP inhibitor in the last 12 months prior to LDL-C screening.
  • Type 1 diabetes or poorly controlled type 2 diabetes (HbA1c > 9%)
  • Treatment for more than 2 weeks in the last 3 months prior to LDL-C screening with systemic cyclosporine/steroids/vitamin A or retinol derivatives for the treatment of dermatologic conditions
  • Thyroid stimulating hormone (TSH) < lower limit of normal or > 1.5x upper limit of normal (unless below LLN, treated and in clinically euthyroid state)
  • Moderate to severe renal dysfunction
  • Active liver disease or hepatic dysfunction
  • 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
  • Baseline IVUS does not meet IVUS Core Lab technical standards
  • Unreliability as a study participant
  • Currently enrolled in or < 30 days since ending another investigational device / drug study
  • Female subject who has not used an acceptable method(s) of birth control for at least 1 month prior to screening, or who is not willing to inform her partner or her participation in the study, unless the female subject is sterilized or postmenopausal
  • Subject is pregnant or breast feeding, planning to become pregnant, or planning to breastfeed during the study
  • History of malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma)
  • Subject has previously received AMG 145 or any other investigational therapy to inhibit PCSK9
  • Known sensitivity to any of the active substances or their excipients
  • Subject will not be available for protocol-required study visits or procedures
  • Subject is not suitable in the opinion of the investigator

Contact Info:

  • Amgen Call Center
  • 866-572-6436