atherosclerotic cardiovascular disease MedDRA version: 20.0 Level: LLT Classification code 10051615 Term: Atherosclerotic cardiovascular disease System Organ Class: 100000004866
Conditions
Interventions
Trade Name: Repatha
Product Name: Evolocumab
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: EVOLOCUMAB
Other descriptive name: Evolocumab
Concentration unit: mg mil
Sponsors
Friedrich-Alexander-Universtiy Erlangen-Nürnberg, Medical Faculty
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed informed consent in written form - Male or female 40 - 80 years - History of clinically evident atherosclerotic cardiovascular disease as evidenced by ANY of the following: o diagnosis of coronary artery disease as evidenced by acute coronary syndrome, myocardial infarction, coronary stent implantation, coronary stenosis = 50% by coronary angiography. o diagnosis of non-hemorrhagic stroke or transient ischemic attack (TIA) o symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Inability to image the brachial artery and to perform FMD - Subjects with statin intolerance - Known or suspected homozygous FH - Subject must not be randomized within 4 weeks of their most recent MI or stroke - NYHA class III or IV, or last known left ventricular ejection fraction 180 mmHg or pDBP > 110 mmHg - 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 - Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab 1.5 times the upper limit of normal (ULN), respectively, and free thyroxine (T4) levels that are outside normal range at final screening - Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) 3 times the ULN as determined by central laboratory analysis at final screening - Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal) - Personal or family history of hereditary muscular disorders - LDL or plasma apheresis within 12 months prior to randomization - Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years - Creatinine Kinase (CK) > 5 times the ULN at final screening - Known major active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator - 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 - Subject has received drugs via a systemic route that have known major interactions with background statin therapy (see Appendix 14.4., study protocol version 1.6) within 1 month prior to randomization or is likely to require such treatment during the study period - Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or less than 5 fold of half-live time of the investigational drug, or receiving other investigational agent(s) - 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; o 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of subcutaneous (SC) evolocumab compared with placebo on - absolute and percent change of FMD (UNEX EF) after 8 weeks of treatment from baseline. ;Secondary Objective: To evaluate the effect of SC evolocumab compared with placebo on - absolute and percent change of FMD (UNEX EF) after 1 and 4 weeks of treatment from baseline and and across all visits. - absolute and percent change of L-FMC and combined FMD+L-FMC (UNEX EF) after 1, 4 and 8 weeks of treatment from baseline and across all visits. - absolute and percent change of pSBP, pDBP (Dinamap ), cSBP, cDBP, cPP, cAP, Pf, Pb, cAIx(@75) and PWV assessed on-site (Sphygmocor™) after 1, 4 and 8 weeks of treatment from baseline and across all visits. - absolute and percent change of pSBP, pDBP, cSBP, cDBP, cPP, cAP, Pf, Pb, cAIx(@75) and PWV assessed over 24 hours (Mobil-O-Graph®) after 1, 4 and 8 weeks of treatment from baseline and across all visits. - absolute and percent change of LDL-C, Lp(a), non HDL-C, and triglycerides after 1, 4 and 8 weeks of treatment from baseline and across all visits. ;Primary end point(s): Effect of subcutaneous (SC) evolocumab compared with placebo on - absolute and percent change of FMD (UNEX EF) after 8 weeks of treatment from baseline. ;Timepoint(s) of evaluation of this end point: before and after 8 weeks of treatment (parallel-arm study) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Effect of SC evolocumab compared with placebo on - absolute and percent change of FMD (UNEX EF) after 1 and 4 weeks of treatment from baseline and and across all visits. - absolute and percent change of L-FMC and combined FMD+L-FMC (UNEX EF) after 1, 4 and 8 weeks of treatment from baseline and across all visits. - absolute and percent change of peripheral systolic BP (pSBP), peripheral diastolic BP (pDBP) (Dinamap ), cSBP, central diastolic BP (cDBP), central pulse pressure (cPP), central augmentation pressure (cAP), forward pressure amplitude (Pf), backward pressure amplitude (Pb), central augmentation index (cAIx, also normalized to a heart rate of 75 beats per minute [cAIx@75]) and PWV assessed on-site (Sphygmocor™) after 1, 4 and 8 weeks of treatment from baseline and across all visits. - absolute and percent change of pSBP, pDBP, cSBP, cDBP, cPP, cAP, Pf, Pb, cAIx(@75) and PWV assessed over 24 hours (Mobil-O-Graph®) after 1, 4 and 8 weeks of treatment from baseline and across all visits. - absolute and percent change of LDL-C, lipoprotein(a) [Lp(a)], non-high-density lipoprotein cholesterol (non HDL-C), and triglycerides after 1, 4 and 8 weeks of treatment from baseline and across all visits. ;Timepoint(s) of evaluation of this end point: before and after 1, 4 and 8 weeks of treatment (parallel-arm study) | — |
Countries
Germany
Contacts
Public ContactClinical Resarch Unit
Medizinische Klinik 4, Friedrich-Alexander University Erlangen-Nürnberg
Outcome results
None listed