acute coronary syndrome
Conditions
Interventions
Product Name: MDCO-216
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rApoA-IM Protein (dimer)
CAS Number: 1508281-61-5
Current Sponsor code: MDCO-216
Other descriptiv
Sponsors
The Medicines Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female subjects greater than or equal to 18 years of age 2.Have experienced a recent ACS event within 14 days of randomization that requires a clinically indicated coronary angiogram 3.A qualifying ACS event is defined as a spontaneous MI: A diagnosis of a qualifying MI event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or creatinine kinase-myocardial isoenzyme band [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 (greater than or equal to 10 minutes) at rest within 24 hours prior to hospitalization for MI •New electrocardiogram (ECG) findings (or presumed new if no prior ECG available) indicative of acute myocardial ischemia in absence of left ventricular hypertrophy and left bundle branch block (LBBB) as listed: -New or presumed new ST depression greater than 0.5 millimeters (mm) in two contiguous leads or T-wave inversion greater than 1 mm in leads with predominant R wave or R/S greater than 1mm in two contiguous leads -New 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 -New 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 -New Q waves =30 ms wide and >1mm deep in any 2 leads of a contiguous lead grouping or Q wave >20 ms or QS complex in leads V2 and V3 (These criteria also apply to silent MI detected during a routine follow-up visit) •Loss 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, magnetic resonance imaging) 4.Baseline coronary angiogram must meet all of the following criteria for IVUS interrogation of Target Artery: TARGET ARTERY: •Must be accessible to the IVUS catheter •Must have a stenotic area of =20% and =65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1.Baseline IVUS not completed due to non-qualifying coronary angiogram as demonstrated by: •Greater than 50% reduction in lumen of the left main coronary artery by visual estimation •Extensive CAD with no target vessel for IVUS interrogation 2.Baseline IVUS interrogation determined to be unacceptable by the Atherosclerosis Imaging Core Laboratory 3.Clinically significant heart disease which, in the opinion of the investigator, is likely to require CABG, PCI, cardiac transplantation, and 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) 4.New York Heart Association class III or IV heart failure or last known left ventricular ejection fraction less than 30% 5.Coronary artery bypass surgery less than 6 weeks prior to the qualifying IVUS 6.Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication 7.Uncontrolled severe hypertension: systolic blood pressure greater than 180 mmHg or diastolic blood pressure > 110 mmHg prior to randomization despite antihypertensive therapy 8.Poorly controlled diabetes mellitus and an HbA1c greater than 10.0% prior to randomization 9.Active liver disease defined as any known current infectious, neoplastic or metabolic pathology of the liver OR unexplained alanine aminotransferase, aspartate aminotransferase, elevation greater than 2 × ULN OR total bilirubin elevation greater than1.5 × ULN at screening confirmed by a repeat measurement at least 1 week apart 10.Fasting triglyceride value less than 400 mg/deciliter (dL) 11.Impaired kidney function defined as calculated glomerular filtration rate less than 60 milliliter (mL)/min by Modification of Diet in Renal Disease formula. In addition, subjects with a 0.3 mg/dL or 25% increase in serum creatinine in the initial 3 to 5 days from presentation for ACS will be excluded from the study 12.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 greater than 3 years before screening 13.Body weight greater than 120 kg or less than 20 kg 14.Women who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device or tubal ligation). Women who are greater than 2 years postmenopausal (defined as greater than or equal to 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 15.Men who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide) 16.Previous participation in this study or any preceding study with ETC-216, MDCO-216, or similar investigational medicines containing apolipoprotein A-I (ApoA-I) proteins 17.Known allergy to the phospholipid or any other component of the investigational product (dimeric rApoA-IM, 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, or mannitol and sucrose in phosphate buffer). 18.Treatment with other investigational medicinal products or devices within 30
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of MDCO-216 treatment on the change in PAV of a target coronary artery, as measured by IVUS imaging, following MDCO-216 compared with placebo in subjects with CAD and a recent ACS event in order to establish safety and the dose and regimen for Phase III clinical trials.;Secondary Objective: To evaluate the effect of MDCO-216 on the following additional atheroma parameters measured by IVUS: - Change in TAV from baseline to Day 36 post randomization - Change in TAV in the 10 mm subsegment with the greatest disease burden at baseline - Proportion of subjects who demonstrate regression of coronary atherosclerosis, defined as reduction in PAV from baseline to Day 36 of more than 2 standard deviations (SD) of the test/re-test variability. - Proportion of subjects who demonstrate regression of coronary atherosclerosis, defined as a change in PAV from baseline to Day 36 of less than zero (ie, any reduction in PAV from baseline);Primary end point(s): Change in PAV from baseline to Day 36 post randomization, as determined by IVUS;Timepoint(s) of evaluation of this end point: baseline, D36 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Change in TAV from baseline to Day 36 post randomization, as determined by IVUS •Change in TAV for the 10 mm subsegment with the greatest disease burden at baseline •Proportion of subjects in each group who demonstrate regression of coronary atherosclerosis, defined as reduction in PAV from baseline to Day 36 of more than two SD of the test/re-test variability. •Proportion of subjects in each group with regression of coronary atherosclerosis, defined as a change in PAV from baseline to Day 36 of less than zero (ie, any reduction in PAV) ;Timepoint(s) of evaluation of this end point: baseline, D36 | — |
Countries
Australia, Canada, Czech Republic, Germany, Hungary, Netherlands, New Zealand, Poland, Spain, United States
Contacts
Public ContactGlobal Health Science Center
The Medicines Company
Outcome results
None listed