GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound

Study Overview
=================
Brief Summary
-----------------
This study will evaluate whether low-density lipoprotein (LDL-C) lowering with evolocumab (AMG 145) results in greater change from baseline in percent atheroma volume (PAV) at week 78 than placebo in adults with coronary artery disease taking lipid lowering therapy.

Official Title
-----------------
A Double-blind, Randomized, Multi-center, Placebo-controlled, Parallel-group Study to Determine the Effects of Evolocumab (AMG 145) Treatment on Atherosclerotic Disease Burden as Measured by Intravascular Ultrasound in Subjects Undergoing Coronary Catheterization

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Biological: Evolocumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical indication for coronary angiography Subjects already taking statin therapy, niacin or ezetimibe at screening must have been on a stable dose for at least 4 weeks prior to screening LDL-C. Subjects not taking lipid-regulating therapy must enter the study via a lipid stabilization period. Subjects who are intolerant to statins must meet statin intolerance entry criteria Fasting LDL-C ≥ 80 mg/dL (2.07 mmol/L) with or without additional risk factors, or, LDL-C ≥ 60 -< 80 mg/dL (1.55-2.07 mmol/L) in the presence of one major or three minor risk factors Subjects must meet the following criteria at the qualifying coronary catheterization procedure: Evidence of coronary heart disease (at least one lesion in a native coronary artery that has > 20% reduction in lumen diameter) or prior percutaneous intervention (PCI) Left main coronary artery < 50% reduction in lumen diameter by visual estimation Target coronary artery for IVUS must be accessible to the IVUS catheter, must not have a > 50% reduction in lumen diameter within the target segment (and at least 40 mm in length); cannot have undergone prior PCI or coronary artery bypass graft (CABG) and is not a candidate for intervention over the next 18 months. It may not be a bypass graft, bypassed vessel or culprit vessel for previous myocardial infarction (MI). Exclusion Criteria: Coronary artery bypass graft surgery < 6 weeks prior to the qualifying IVUS New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction less than 30% Uncontrolled cardiac arrhythmia that is not controlled by medications in the 3 months prior to randomization Known hemorrhagic stroke Uncontrolled hypertension at randomization Fasting Triglycerides ≥ 400 mg/dL (4.5 mmol/L) at screening Type 1 diabetes or poorly controlled type 2 diabetes (hemoglobin A1c [HbA1c] > 9%) at screening. Moderate to severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73m²) at screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo to evolocumab administered by subcutaneous injection once a month for 76 weeks. | Drug: Placebo<br>* Administered by subcutaneous injection<br>|
| Experimental: Evolocumab<br>Participants received 420 mg evolocumab administered by subcutaneous injection once a month for 76 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percent Atheroma Volume at Week 78 | Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma. | Baseline and week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Regression in Total Atheroma Volume | Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. Total atheroma volume (TAV) in a ≥ 40 mm segment of the targeted coronary artery was calculated as the average plaque area over the number of images that were evaluated by IVUS multiplied by the median vessel length to compensate for differences in segment length between participants. Regression in TAV was defined as any reduction from baseline in TAV. | Baseline and week 78 | 
| Change From Baseline in Total Atheroma Volume at Week 78 | Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. Total atheroma volume (TAV) in a ≥ 40 mm segment of the targeted coronary artery was calculated as the average plaque area over the number of images that were evaluated by IVUS multiplied by the median vessel length to compensate for differences in segment length between participants. | Baseline and week 78 | 
| Percentage of Participants With Regression in Percent Atheroma Volume | Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma. Regression in PAV was defined as any reduction from baseline in PAV. | Baseline and week 78 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cholesterol, High Cholesterol, Elevated Cholesterol, Raised Cholesterol