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

Amgen

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: Placebo; Biological: Evolocumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01813422

2012-004208-37 (EudraCT Number)

20120153

Details and patient eligibility

About

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.

Enrollment: 970 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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970 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo to evolocumab administered by subcutaneous injection once a month for 76 weeks.

Treatment:

Drug: Placebo

Evolocumab

Experimental group

Description:

Participants received 420 mg evolocumab administered by subcutaneous injection once a month for 76 weeks.

Treatment:

Biological: Evolocumab