acute coronary syndrome
Conditions
Interventions
Product Code: MDCO-216
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rApoA-IM Protein (dimer)
Current Sponsor code: MDCO-216
Other descriptive name: rApoA-IM
Concen
Sponsors
The Medicines Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female subjects = 18 years of age. 2) Have experienced a recent 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 =65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: 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 180 mmHg or diastolic blood pressure > 110 mmHg prior to randomization despite anti-hypertensive therapy. 9) Poorly controlled diabetes mellitus and an HbA1c > 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 > 2x ULN OR total bilirubin elevation > 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 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 orfive half?lives, whichever is longer. 20) Known history of alcohol and/or drug abuse. 21) Use of other investigational medicinal produc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of MDCO-216 treatment on the change in percent atheroma volume (PAV) of a target coronary artery as measured by intravascular ultrasound (IVUS) imaging following five weekly infusions of MDCO-216 in subjects with a recent acute coronary syndrome. ;Secondary Objective: •To evaluate the effect of MDCO-216 on the following additional atheroma parameters measured by IVUS: o change in total atheroma volume (TAV); o change in TAV in the 10 mm subsegment containing the most amount of disease at baseline; o proportion of subjects who demonstrate regression of coronary atherosclerosis, defined as a change PAV of less than zero (ie, an reduction in PAV) and an additional analysis of those with more than two standard deviations of the test/re-test variability. ;Primary end point(s): The primary endpoint is defined as change from baseline to study end (Day 36 post-randomization) in coronary PAVas determined by IVUS. ;Timepoint(s) of evaluation of this end point: baseline, D36 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this trial are: •Change in TAV from baseline to Day 36 post-randomization, as determined by IVUS •The proportion of subjects in each group with regression of coronary atherosclerosis, defined as a reduction in PAV from baseline to Day 36 of more than 2 standard deviations of the test-retest 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. •Change in TAV for the 10-mm subsegment with the greatest disease burden at baseline;Timepoint(s) of evaluation of this end point: baseline, D36 | — |
Countries
Canada, Czech Republic, Hungary, Netherlands, Poland
Contacts
Public ContactGlobal Health Science Center
The Medicines Company
Outcome results
None listed