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 percent atheroma volume (PAV) at week 78 than placebo in subjects with coronary artery disease taking lipid lowering therapy.

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