Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if bempedoic acid (ETC-1002) 180mg added to PCSK9 inhibitor (evolocumab) therapy is effective and safe in patients with elevated LDL cholesterol.

Official Title
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A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg QD When Added to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)-Inhibitor Therapy

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: bempedoic acid 180mg
* Other: placebo
* Drug: evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years or legal age of majority depending on regional law Fasting, calculated LDL-C at screening ≥160 mg/dL and following PCSK9i therapy ≥70 mg/dL Men and nonpregnant, nonlactating women Exclusion Criteria: Heterozygous (HeFH) or Homozygous (HoFH) Familial Hypercholesterolemia Total fasting TG ≥500 mg/dL Renal dysfunction or a glomerulonephropathy; eGFR <30 mL/min/1.73 m2 Known cardiovascular disease (CVD), peripheral arterial disease (PAD), or cerebrovascular disease (CD) History of type 1 or type 2 diabetes Uncontrolled hypertension Uncontrolled hypothyroidism Liver disease or dysfunction Gastrointestinal conditions or procedures (including Lap-Band® or gastric bypass) History of hematologic or coagulation disorders History of malignancy (except non-metastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ) Unexplained creatine kinase (CK) >3 × ULN Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to screening, such as: anacetrapib, dalcetrapib, or evacetrapib Pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 30 days after the end of treatment

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bempedoic acid<br>Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly | Drug: bempedoic acid 180mg<br>* Daily bempedoic acid 180mg tablet in addition to monthly PCSK9i (evolocumab) background therapy<br>* Other names: ETC-1002;Drug: evolocumab<br>* Monthly PCSK9i (evolocumab) background therapy<br>* Other names: Repatha;|
| Placebo Comparator: placebo<br>Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly | Other: placebo<br>* Daily matching placebo tablet in addition to monthly PCSK9i (evolocumab) background therapy<br>Drug: evolocumab<br>* Monthly PCSK9i (evolocumab) background therapy<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 Month 2 | Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA), with treatment group as a factor and Baseline as a covariate. Missing data were imputed using last observation carried forward (LOCF) (only post-Baseline values were carried forward). | Baseline; Month 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in LDL-C at Month 1 | Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis. | Baseline; Month 1 | 
| Absolute Change From Baseline in LDL-C at Month 1 and Month 2 | Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the average of the Screening Visit 4 and the Day 1 value. If only 1 value is available, then that single value is used as Baseline. Change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF. | Baseline; Month 1 and Month 2 | 
| Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2 | Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline apolipoprotein B (apoB) is defined as the Day 1 value. Baseline total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) are defined as the average of the Month -1 (Screening Visit 4) and the Day 1 (Treatment Visit 1) values. If a missing value presented at Month -1 or Day 1, then the last non-missing value prior to the first dose of double-blind study medication (including unscheduled assessments) within Month -1 and Day 1 was used to compute the Baseline measurements. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF. | Baseline; Month 1 and Month 2 | 
| Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2 | Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the Day 1 value. Percent change from Baseline was analyzed using a non-parametric approach. Missing Month 2 data were handled by LOCF. Observed data were used for analysis at Month 1. | Baseline; Month 1 and Month 2 | 
| Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE) | Treatment-emergent AEs (TEAEs) and SAEs (TESAEs) were reported and defined as any AE that began or worsened after the first dose of investigational medicinal product. | up to Month 2 (until 30 days after last dose) | 
| Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3x the Upper Limit of Normal (ULN) at Month 1 and Month 2 | The number of participants with ALT or AST >3x ULN was measured. | Month 1 and Month 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholesterol, PCSK9, Repatha, evolocumab, LDL-C