A placebo-controlled, double-blind, randomized trial to compare the effect of treatment on plaque burden as determined by intravascular ultrasound and to evaluate the efficacy, pharmacokinetics, safety, and tolerability of MDCO-216 given as multiple weekly infusions in subjects with a recent acute coronary syndrome.
- Conditions
- Atherosclerosis and plaque burden1001108210003216
- Registration Number
- NL-OMON43722
- Lead Sponsor
- Medicines Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 29
1)Male or female subjects * 18 years of age.
2)Have experienced a recent Acute Coronary Syndrome (ACS) event within 14 days of screening that requires a clinically indicated coronary angiogram.
3)A qualifying ACS event will be defined as follows:
A diagnosis of a qualifying MI event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or CK-MB mass) with at least one determination greater than the 99th percentile or upper limits of normal for the laboratory and at least one of the following:;*Chest discomfort or symptoms of myocardial ischemia (* 10 minutes) at rest within 24 hours prior to hospitalization for MI.;*New ECG findings (or presumed new if no prior ECG available) indicative of acute myocardial ischemia in absence of left ventricular hypertrophy (LVH) and left bundle branch block (LBBB) as listed:;oNew or presumed new ST depression greater than 0.5 mm in 2 contiguous leads or T wave inversion greater than 1mm in leads with predominant R wave or R/S greater than 1 in 2 contiguous leads.;oNew or presumed new ST elevation at the J point in * 2 contiguous leads with the cut-off points: * 0.2 mV in men or * 0.15mV in women in leads V2-V3 and/or *0.1 mV in other leads or new or presumed new LBBB.;oNew tall R wave > 40 ms in V1, V2 and R/S * 1 in V1 with concordant positive T-wave in the absence of a conduction defect.;oNew Q waves * 30 ms wide and > 1mm deep in any 2 leads of a contiguous lead grouping or Q wave > 20ms or QS complex in leads V2 and V3 (These criteria also apply to silent MI detected during a routine follow-up visit).;oLoss of viable myocardium based on imaging evidence of new or presumed new wall motion or perfusion deficit (eg, echocardiography, left ventriculography during cardiac catheterization radionuclide angiography, single-photon emission tomography, MRI).;4)Baseline coronary angiogram must meet all of the following criteria for IVUS interrogation of TARGET ARTERY:;*Must be accessible to the IVUS catheter.;*Must have a stenotic area of * 20% and < 50% in lumen diameter by angiographic visual estimation within the length of the native coronary artery (*target segment*) for imaging by IVUS.;*The target artery has not undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).;*The target artery is not currently a candidate for intervention or a likely candidate for intervention over the treatment phase of the study and until the second IVUS interrogation at Day 36.;*The target artery may not be a bypass graft.;*The target artery may not be the culprit vessel for a previous MI.;*TARGET ARTERY MAY HAVE:;oA lesion of up to 60% stenosis, distal to the target segment, provided that this area is not a target for PCI or CABG.;oA single branch of the *target vessel* may have a narrowing * 70% by visual estimation, provided that the branch in question is not a target for PCI or CABG.;5)Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
1) Baseline IVUS not completed due to non-qualifying coronary angiogram as demonstrated by:
a) Greater than 50% reduction in lumen of the left main coronary artery by visual estimation.
b)Extensive CAD with no target vessel for IVUS interrogation.
2) Baseline IVUS interrogation determined to be unacceptable by the Atherosclerosis Imaging Core Laboratory (AICL).
3) Previous STEMI within the last 90 days (not including qualifying ACS event)
4) Clinically significant heart disease which, in the opinion of the Investigator, is likely to require CABG, PCI cardiac transplantation, surgical or percutaneous valve repair and/or replacement following index IVUS imaging (does not apply to PCI that occurs as a result of initial screening angiogram and completed prior to index IVUS imaging).
5) New York Heart Failure Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction less than 30%.
6)Coronary artery bypass surgery < 6 weeks prior to the qualifying IVUS.
7)Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication.
8)Uncontrolled severe hypertension: systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg prior to randomization despite anti-hypertensive therapy.
9)Poorly controlled diabetes mellitus and an HbA1c greater than 10.0% prior to randomization.
10)Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver OR alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation greater 2x ULN OR total bilirubin elevation greater than 1.5x ULN at screening confirmed by a repeat measurement at least one week apart.
11)Fasting triglyceride value > 400 mg/dL.
12)Impaired kidney function defined as calculated glomerular filtration rate < 60 mL/min by eGFR. In addition, subjects with a 0.3 mg/dL or 25% increase in serum creatinine in the initial 3-5 days following angiography will be excluded from the study.
13)Serious comorbid disease in which the life expectancy of the subject is shorter than the duration of the trial (eg, acute systemic infection, cancer, or other serious illnesses). This includes all cancers with the exception of treated basal-cell carcinoma occurring > 3 years before screening.
14)Body weight > 120 kg.
15)Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device or tubal litigation). Women who are > 2 years postmenopausal defined as * 1 year since last menstrual period AND if less than 55 years old with a negative pregnancy test within 24 hours of randomization or surgically sterile are exempt from this exclusion.
16)Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).
17)Previous participation in this study or any preceding study with ETC-216, MDCO-216, or similar investigational medicines containing ApoA-I proteins.
18)Known allergy to the phospholipid or any other component of the investigational product (dimeric rApoA-IM, POPC, or mannitol and sucrose in phosphate buffer)
19)Treatment with other investigational medicinal products or devices within 30 days orfivehalf*lives, whichever is longer.
20)Known hist
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary outcome of this trial is the change in PAV from baseline to Day 36<br /><br>post randomization, as determined by IVUS.<br /><br>The primary variable of change in PAV will be computed as follows: PAV (Week 6)<br /><br>* PAV (baseline)</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary outcome trial are:<br /><br>-Change in TAV from baseline to Day 36 post-randomization, as determined by IVUS<br /><br>-Change in TAV for the 10 mm subsegment with the greatest disease burden at<br /><br>baseline<br /><br>-The proportion of subjects in each group with regression of coronary<br /><br>atherosclerosis, defined as a reduction in PAV from baseline to Day 36 of more<br /><br>than 2 standard deviations of the test-retest variability.<br /><br>-Proportion of subjects in each group with regression of coronary<br /><br>atherosclerosis, defined as a change in PAV from baseline to Day 36 of less<br /><br>than zero.</p><br>