LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy

Study Overview
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Brief Summary
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To evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab (AMG 145) administered every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on percent change from baseline in LDL-C when used in addition to a statin in adults with hypercholesterolemia.

Official Title
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LAPLACE TIMI 57 - A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With HMG-CoA Reductase Inhibitors in Hypercholesterolemic Subjects

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Biological: Evolocumab
* Other: Placebo to Evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 to ≤ 80 years of age On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks Fasting LDL-C ≥ 85 mg/dL Fasting triglycerides ≤ 400 mg/dL Exclusion Criteria: Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (Glycosyated Hemoglobin (HbA1c) > 8.5%) Uncontrolled hypertension New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction < 30% Uncontrolled cardiac arrhythmia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Q2W<br>Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. | Other: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Placebo Comparator: Placebo Q4W<br>Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. | Other: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Experimental: Evolocumab 70 mg Q2W<br>Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 105 mg Q2W<br>Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 140 mg Q2W<br>Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 280 mg Q4W<br>Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 350 mg Q4W<br>Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 420 mg Q4W<br>Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LDL-C at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 | 
| Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 |  | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9)