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

The Medicines Company0 sites126 target enrollmentDecember 3, 2015

ConditionsAcute Coronary Syndrome

InterventionsMDCO-216 Placebo

DrugsMDCO-216 Placebo

Overview

Phase: Phase 1
Intervention: MDCO-216
Conditions: Acute Coronary Syndrome
Sponsor: The Medicines Company
Enrollment: 126
Primary Endpoint: Change From Baseline In Percent Atheroma Volume (PAV) At Day 36
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This study will be a proof-of-concept, placebo-controlled, double-blind, randomized trial in participants with a recent acute coronary syndrome (ACS) to evaluate the efficacy, pharmacokinetics, safety, tolerability, disease progression measures by IVUS, and pharmacodynamics of MDCO-216 infusion. Eligible participants will be randomized to receive 5 infusions of MDCO-216 20 milligrams/kilogram (mg/kg) or placebo in a 1:1 ratio.

Registry

clinicaltrials.gov

Start Date

December 3, 2015

End Date

October 26, 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

The Medicines Company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have experienced a recent ACS event within 14 days of screening that requires a clinically indicated coronary angiogram.
•A qualifying ACS event will be defined as follows: a diagnosis of a qualifying myocardial infarction (MI) event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or creatine kinase myoglobin \[CK-MB\] mass) with at least one determination greater than the 99th percentile or upper limits of normal (ULN) 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 and/or new electrocardiogram (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 (LBB).
•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
•Target artery 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
•Target artery has not undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
•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
•Target artery may not be the culprit vessel for a previous MI.
•The target artery may have the following:
•A lesion of up to 60% stenosis, distal to the target segment, provided that this area is not a target for PCI or CABG

Exclusion Criteria

•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, or extensive coronary artery disease (CAD) with no target vessel for IVUS interrogation.
•Baseline IVUS interrogation determined to be unacceptable by the Atherosclerosis Imaging Core Laboratory.
•ST-segment elevation myocardial infarction (STEMI) within the last 90 days
•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).
•New York Heart Failure Association Class III or IV heart failure or last known left ventricular ejection fraction \<30%.
•Coronary artery bypass surgery \<6 weeks prior to the qualifying IVUS.
•Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication.
•Uncontrolled severe hypertension: systolic blood pressure \>180 millimeters of mercury (mmHg) or diastolic blood pressure \>110 mmHg prior to randomization despite anti-hypertensive therapy.
•Poorly controlled diabetes mellitus and a hemoglobin A1c (HbA1c) \>10.0% prior to randomization.
•Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or alanine aminotransferase, aspartate aminotransferase elevation \>2 x ULN or total bilirubin elevation \>1.5 x ULN at screening confirmed by a repeat measurement at least one week apart.

Arms & Interventions

MDCO-216

20 mg/kg of MDCO-216 administered intravenously (IV) as a 360 milliliter (mL) infusion over 2 hours on Days 1, 8, 15, 22, and 29

Intervention: MDCO-216

Placebo

360 mL of placebo (0.9% sodium chloride \[NaCl\] solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline In Percent Atheroma Volume (PAV) At Day 36

Time Frame: Baseline, Day 36

Change from Baseline to Day 36 post-randomization in PAV in a targeted (imaged) coronary artery for all anatomically comparable slices, as determined by IVUS. The change is calculated by subtracting the value at Baseline from the value at Day 36, with positive numbers to represent increases and negative numbers to represent decreases. Change in PAV was analyzed using an analysis of covariance (ANCOVA) model that included Baseline PAV as a covariate and treatment group as factor. Least Squares (LS) mean was adjusted for stratification factors of country and prior statin use.

Secondary Outcomes

Change From Baseline In Total Atheroma Volume (TAV) At Day 36(Baseline, Day 36)
Change From Baseline In TAV For The 10 Millimeters (mm) Subsegment With The Greatest Disease Burden At Day 36(Baseline, Day 36)
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change <0(Baseline through Day 36)
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change Greater Than 2 Standard Deviations Of Test-Retest Measurement Variability(Baseline through Day 36)