The Effects of Evolocumab in Patients With Diabetes and Atherosclerotic Vascular Disease

Inclusion Criteria

• Subjects ≥18 years of age signing of informed consent;
• A history of clinical ASCVD, which is defined as: acute coronary syndrome, or a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease presumed to be of atherosclerotic origin;
• Clinical diagnosis of type 2 diabetes according to ADA/ CDA guidelines;
• Subject on stable dose of maximally-tolerated statin therapy for ≥4 weeks prior to screening and LDL-c ≥70mg/dL. For subjects whose maximally tolerated dose of statin is no type or dose (i.e. determined to be statin intolerant by primary investigator), background lipid-lowering therapy is not required;
• Fasting triglycerides ≤400mg/dL (4.52mmol/L) by central laboratory at screening;
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures;
• Abnormal urinary Albumin Creatinine Ratio (ACR) as defined by an ACR ≥2;
• Subject tolerates screening placebo injection.

Exclusion Criteria

• Personal or family history of hereditary muscular disorders;
• NYHA III or IV heart failure, or last know left ventricular ejection fraction (LVEF) 10%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting serum glucose ≥126mg/dL [7.0mmol/L] or HbA1c ≥6.5% without prior diagnosis of diabetes;
• Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) >160mmHg or diastolic BP (DBP) >100mmHg;
• Subject who has taken a cholesterol easter transfer protein (CETP) inhibitor in the last 12 months prior to LDL-c screening, such as: anacetrapib, dalcetrapib or evacetrapib;
• Treatment in the last 3 months prior to LDL-c screening with any of the following drugs: systemic cyclosporine, systemic steroids (e.g. IV, intramuscular [IM], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (e.g. Accutane); (Note: vitamin A in a multivitamin preparation is permitted). Topical retinol prescription and non-prescription derivatives or creams are permitted;
• Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) 1.5 times the ULN, respectively, at screening. Potential subjects with TSH 3 times the ULN as determined by central laboratory analysis at screening;
• Known active infection or major hematologic, renal metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator;
• Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months prior to randomization;
• Unreliability as a study participant based on the investigator's (or designee's) knowledge of the subject (e.g. alcohol or other drug abuse);
• 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 has either (1) not used at least 1 highly effective method of contraception for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal;
• Subject who is pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 15 weeks after the end of treatment;
• Use of PCSK9 inhibitor within 10 weeks from screening;
• Subject who has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures;
• Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years;
• Subject who has known sensitivity to any of the products or components to be administered during dosing;