A Study Assessing the Impact of Additional LDL-Cholesterol Reduction on Major Cardiovascular Events when Evolocumab (AMG 145) is used in combination With Statin Therapy In Patients with Clinically Evident Cardiovascular Disease
- Conditions
- DyslipidemiaMedDRA version: 18.1Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 100000004861MedDRA version: 18.1Level: LLTClassification code 10058110Term: DyslipidemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2012-001398-97-SK
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 27564
4.1.1 Signed informed consent
4.1.2 Male or female = 40 to = 85 years of age at signing of informed consent
4.1.3 History of clinically evident cardiovascular disease as evidenced by ANY
of the following:
o diagnosis of myocardial infarction
o diagnosis of non-hemorrhagic stroke (TIA does not qualify as
stroke for inclusion)
o symptomatic peripheral arterial disease (PAD), as evidenced
by intermittent claudication with ankle-brachial index
(ABI) < 0.85, or peripheral arterial revascularization
procedure, or amputation due to atherosclerotic disease
Note: the proportion of subjects with history of MI or nonhemorrhagic stroke > 5 years prior to screening will be determined by the sponsor
4.1.4 At least 1 major risk factor or at least 2 minor risk factors below:
Major Risk Factors (1 Required):
o diabetes (type 1 or type 2)
o age = 65 years at randomization (and = 85 years at time of
informed consent)
o MI or non-hemorrhagic stroke within 6 months of screening
o additional diagnosis of myocardial infarction or non-hemorrhagic
stroke excluding qualifying MI or non-hemorrhagic stroke (a)
o current daily cigarette smoking
o history of symptomatic PAD (intermittent claudication with ABI
< 0.85, or peripheral arterial revascularization procedure, or
amputation due to atherosclerotic disease) if eligible by MI or
stroke history
Minor Risk Factors (2 Required):
o history of non-MI related coronary revascularization (a)
o residual coronary artery disease with = 40% stenosis in = 2 large vessels
o Most recent HDL-C < 40 mg/dL (1.0 mmol/L) for men
and < 50 mg/dL (1.3 mmol/L) for women by central laboratory
before randomization
o Most recent hsCRP > 2.0 mg/L by central laboratory before
randomization
o Most recent LDL-C = 130 mg/dL (3.4 mmol/L) or non-HDL-C
= 160 mg/dL (4.1 mmol/L) by central laboratory before
randomization
o metabolic syndrome (b)
4.1.5 Most recent fasting LDL-C = 70 mg/dL (= 1.8 mmol/L) or non-HDL-C
= 100 mg/dL (= 2.6 mmol/L) by central laboratory during screening after = 2 weeks of stable lipid lowering therapy per Appendix E
4.1.6 Most recent fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory before randomization
(a)Note: there is no time limit on additional qualifying medical history.
(b)Definition: metabolic syndrome for this protocol is defined as = 3 of the following (Alberti et al, 2009):
• waist circumference > 102 cm (> 40 in.) for men and > 88 cm (> 35 in.) for women (Asian men, including Japanese > 90 cm; Asian women, except Japanese > 80 cm; Japanese women > 90 cm)
• triglycerides = 150 mg/dL (1.7 mmol/L) by central laboratory at final screening
• HDL-C < 40 mg/dL (1.0 mmol/L) for men and < 50 mg/dL (1.3 mmol/L) for women by central laboratory at screening (Note: if the HDL-C level is one of criterion used to make the diagnosis of metabolic syndrome, it cannot be used as a separate risk factor)
• systolic blood pressure (SBP) = 130 mmHg or diastolic BP (DBP) = 85 mmHg or hypertension treated with medication
• fasting glucose = 100 mg/dL (= 5.6 mmol/L) by central laboratory at final screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12375
4.2.1 Subject must not be randomized within 4 weeks of their most recent MI or stroke
4.2.2 NYHA class III or IV, or last known left ventricular ejection fraction < 30%
4.2.3 Known hemorrhagic stroke at any time
4.2.4 Uncontrolled or recurrent ventricular tachycardia
4.2.5 Planned or expected cardiac surgery or revascularization within 3 months after randomization
4.2.6 Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg
4.2.7 Use of cholesteryl ester transfer protein (CETP) inhibition treatment, mipomersen, or lomitapide within 12 months prior to randomization. Fenofibrate therapy must be stable for at least 6 weeks prior to final screening at a dose that is appropriate for the duration of the study in the judgment of the investigator. Other fibrate therapy (and derivatives) are prohibited
4.2.8 Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab < 12 weeks prior to final lipid screening
4.2.9 Untreated or inadequately treated hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) < lower limit of normal (LLN) or > 1.5 times the upper limit of normal (ULN), respectively, and free thyroxine (T4) levels that are outside normal range at final screening
4.2.10 Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 at final screening
4.2.11 Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN as determined by central laboratory analysis at final screening
4.2.12 Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal)
4.2.13 Personal or family history of hereditary muscular disorders
4.2.14 LDL or plasma apheresis within 12 months prior to randomization
4.2.15 Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years
4.2.16 CK > 5 times the ULN at final screening
4.2.17 Known major active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator
4.2.18 Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 10 years
4.2.19 Subject has received drugs via a systemic route that have known major interactions with background statin therapy (see Appendix F) within 1 month prior to randomization or is likely to require such treatment during the study period
4.2.20 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)
4.2.21 Female subject who has either (1) not used acceptable method(s) of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment with IP and for an additional 15 weeks after the end of treatment with IP, unless the 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 subject has undergone bilateral oophorectomy
• acc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method