Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

Kastle Therapeutics, LLC58 enrolled

Overview

The purpose of the study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in treating severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for coronary heart disease (CHD). Mipomersen is an antisense drug that reduces a protein in the liver cells called apolipoprotein B (Apo-B). Apo-B plays a role in producing low density lipoprotein cholesterol (LDL-C) (the "bad" cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events. The purpose of this study is to determine whether mipomersen safely and effectively lowers LDL-C in severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hypercholesterolemia Coronary Heart Disease

Interventions

MipomersenDRUG

200 mg (1 mL), weekly subcutaneous injections for 26 weeks

PlaceboDRUG

1 mL weekly subcutaneous injections for 26 weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Fasting LDL-C ≥200 mg/dL (5.1 mmol/L) at screening and the presence of at least 1 of the following criteria: * Myocardial infarction (MI) * Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) * Coronary artery disease documented by angiography or any other accepted imaging technique * Positive exercise test (≥1 mm ST-depression at maximal exercise or test terminated because of angina) or a perfusion defect (e.g., thallium or single photon emission computed tomography) * Other clinical atherosclerotic diseases: peripheral artery disease, symptomatic carotid artery disease, abdominal aortic aneurysm * Or, if alternative above were not met, fasting LDL-C ≥300 mg/dL (7.8 mmol/L) * On stable, maximally tolerated statin therapy for 8 weeks * On stable, medication from an additional class of hypolipidemic agents for 8 weeks. * On stable, low fat diet for 12 weeks * Stable weight for 6 weeks Exclusion Criteria: * Significant health problems in the recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, hypertension, blood disorders, liver disease, cancer, digestive disorders, Type I diabetes, or uncontrolled Type II diabetes * Apheresis within 3 months prior to Screening or expected to start apheresis during the treatment phase

Locations (27)

Unnamed facility

Jupiter, Florida, United States

Unnamed facility

Winter Park, Florida, United States

Outcomes

Primary Outcomes

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point

LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides \>=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

LDL-C at Baseline and the Primary Efficacy Time Point (PET)

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Secondary Outcomes

Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point

Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Apo-B at Baseline and the Primary Efficacy Time Point (PET)

Data from ClinicalTrials.gov

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