Dyslipidemia MedDRA version: 20.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861 MedDRA version: 20.0 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Repatha 420 mg solution for injection in cartridge
Product Name: Evolocumab
Product Code: AMG145
Pharmaceutical Form: Solution for injection in cartridge
INN or Proposed INN: EVOLOCUMAB
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Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria •Age = 18 years at screening. •Clinical indication for coronary angiography during admission due to NSTE-ACS with interventional treatment of culprit plaque. •LDL-C level via local lab assessment based on statin use at screening: - No statin use: = 130 mg/dL - Low- or moderate-intensity statin use: = 80 mg/dL - High-intensity statin use: = 60 mg/dL •On maximally tolerated statin therapy in accordance with standard of care per local guidelines prior to randomization. •Tolerates placebo run-in injection at screening. •Meet all the following criteria at the qualifying coronary angiogram: - Angiographic evidence of coronary artery disease (CAD) with = 20% reduction of lumen diameter by angiographic visual estimation, in addition to the culprit plaque. - Left main coronary artery must not have a > 50% reduction in lumen diameter by visual angiographic estimation. - Targeted vessel: -may not be the culprit vessel for the current or a previous myocardial infarction (MI). -has not undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), and may not be a bypass graft. -may not be a candidate for PCI or CABG currently or over the next 12 months, in the opinion of the investigator. -must be accessible by the OCT catheter. - Targeted segment: -must have up to 50% but not > 50% reduction in lumen diameter by visual angiographic estimation and must be at least 40 mm in length. -must contain at least 1 image with an FCT of = 120 µm and at least 1 image with a lipid arc of > 90° as determined by the imaging core laboratory. -distal plaques of up to 50% stenosis by visual angiographic estimation are permitted, provided that such stenosis is not a target for PCI or CABG. 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 102 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: Subjects are excluded from the study if any of the following criteria apply. •Disease Related: -ST-segment elevation myocardial infarction (STEMI) or left bundle branch block (LBBB). -ACS likely to be caused by a non-atherosclerotic process, in the opinion of the investigator (ie, type 2 myocardial infarction, which is characterized by an imbalance between myocardial oxygen demand and supply). -Clinically significant heart disease which in the opinion of the investigator is likely to require coronary bypass surgery, PCI (does not apply to PCI of non STEMI (NSTEMI) during initial screening angiogram), surgical or percutaneous valve repair and/or replacement during the course of the study. -Any cardiac surgery within 6 weeks prior to screening. •Diagnostic Assessments -Triglycerides = 400 mg/dL (4.5 mmol/L) at screening. -Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 at screening. •Other Medical Conditions -Malignancy except non-melanoma skin cancers, cervical, or breast ductal carcinoma in situ within the last 5 years. -Intolerant to statins as determined by principal investigator. Prior/Concomitant Therapy -Previously received or receiving evolocumab or any other therapy to inhibit PCSK9. -Previously received a cholesterol ester transfer protein (CETP) inhibitor (ie, anacetrapib, dalcetrapib, evacetrapib), mipomersen, lomitapide, or has undergone LDL apheresis in the last 12 months prior to LDL-C screening. •Prior/Concurrent Clinical Study Experience -Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. •Other Exclusions -Baseline OCT does not meet OCT imaging criteria as determined by the imagine core laboratory technical standards. -Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product. (Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.) -Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of investigational product. Refer to Appendix 5 for additional contraceptive information. -Female subject who has not used an acceptable method(s) of birth control for at least 1 month prior to screening, unless the female subject is sterilized or postmenopausal. -Known sensitivity to any of the products or components (eg, carboxymethylcellulose) to be administered during dosing. -Not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject’s and investigator’s knowledge. -Unreliability based on the investigator's (or designee’s) knowledge (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis). -History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of evolocumab on fibrous cap thickness (FCT) in subjects with non ST elevation acute coronary syndrome (NSTE ACS) who are taking maximally tolerated statin therapy.;Secondary Objective: - To evaluate the effects of evolocumab on coronary plaque morphology in subjects with NSTE-ACS who are taking maximally tolerated statin therapy. -Safety: to evaluate the safety and tolerability of evolocumab treatment in subjects with NSTE-ACS who are taking maximally tolerated statin therapy. -Exploratory: •To evaluate the effects of evolocumab on lipid parameters in subjects with NSTE ACS who are taking maximally tolerated statin therapy. •To evaluate the effects of evolocumab on features of coronary plaques in subjects with NSTE ACS who are taking maximally tolerated statin therapy using different imaging techniques. ;Primary end point(s): Absolute change in minimum fibrous cap thickness (FCT) in a matched segment of artery as determined by optical coherence tomography (OCT) from baseline to week 50.;Timepoint(s) of evaluation of this end point: OCT: at screening and week 50 ± 2 week | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Coronary artery segment-based: - Percent change in minimum FCT in a matched segment of artery as determined by OCT from baseline to week 50. - Absolute change in mean minimum FCT for all images assessed in an individual subject as determined by OCT from baseline to week 50. - Absolute change in the maximum lipid arc in a matched segment of artery as determined by OCT from baseline to week 50. 2. Plaque-based: Absolute change in minimum FCT, maximum lipid arc, and lipid core length in lipid rich plaques defined as minimum FCT 90° in at least 3 consecutive images as determined by OCT from baseline to week 50. 3. Safety: Subject incidence of treatment-emergent adverse events and serious adverse events. 4. Exploratory: -Absolute and percent changes in lipid parameters by visit from baseline. -Absolute change in number of microchannels in matched segments of all lesions assessed in an individual subject as determined by OCT from baseline to week 50. -Absolute change in macrophage composition in matched segments of all lesions assessed in an individual subject as determined by OCT from baseline to week 50. -Absolute change in lipid content in matched segments of all lesions assessed in an individual subject as determined by IVUS from baseline to week 50. ;Timepoint(s) of evaluation of this end point: OCT: at screening and week 50 ± 2 week. IVUS: at screening and week 50 ± 2 week. Adverse events and serious adverse events: at screening, day 1, week 4, 12, 24, 36, 50 and 52. Lipid testing: at screening. Fasting lipid testing: at day 1, week 24 and week 50. | — |
Countries
Australia, Czech Republic, Germany, Hungary, Japan, Netherlands, South Africa, United States
Contacts
Public ContactMedical Information
Amgen (EUROPE) GmbH
Outcome results
None listed