A Study of LY3015014 in Participants With High Cholesterol

Eli Lilly and Company527 enrolled

Overview

This study is designed to define the amount and duration of cholesterol lowering and to assess the safety and tolerability of different dose regimens of LY3015014 in participants with high cholesterol. The study will also investigate how the body processes the drug and how the drug affects the body. Participants will remain on a stable diet and will continue taking cholesterol-lowering medications (statins with or without ezetimibe). After signing the informed consent document, the participant will complete a screening/run-in period that will last at most 8 weeks. Then, the treatment period will last approximately 16 weeks. After the treatment period, the participants will complete a follow-up period lasting approximately 8 weeks for a total study duration ranging from approximately 25 to 32 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

527

Conditions

Hypercholesterolemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosed with high low density lipoprotein (LDL) cholesterol * Are on stable daily dose of a statin or have a history of statin intolerance * Men with a partner who can become pregnant must agree to use barrier protection during sexual intercourse to prevent pregnancies * Women who cannot become pregnant, or women who are not pregnant or breast feeding and agree to use a reliable method of birth control to prevent pregnancies Exclusion Criteria: * Have high cholesterol due to another disease or have a rare and serious form of hereditary high cholesterol * Have had recent heart attack, stroke, blood clot or heart surgery, have planned heart or blood vessel surgery, or has a heart that does not pump sufficiently well * Have poorly controlled high blood pressure * Have diabetes that requires an injectable medication (including insulin), or have diabetes that is poorly controlled * Have thyroid blood test that is outside normal range * Have a history of adrenal gland disorder * Have a history of vitamin E deficiency or fat malabsorption syndrome * Have poor kidney function * Have active liver or gall bladder disease, history of hepatitis or liver blood tests that are high * Have a history of muscle disease including muscle damage from a medicine or muscle blood test that is high * Are anemic (low red blood cell counts) * Have a history of allergy or intolerance to other antibody medications * Have a history of human immunodeficiency virus infection (HIV) infection * Are likely to have a major operation or be hospitalized during the study * Have chronic alcohol or drug abuse or dependency * Have or suspected to have any cancer or malignant tumor * Have an active serious infection * Have started or stopped taking a statin or ezetimibe medication, or changed statin dose regimen recently * Are on a statin regimen other than daily dosing (for example, an every-other-day statin regimen) * Have recently used simvastatin (highest dose level), fibrates, bile acid binders, niacin, probucol, or over-the-counter/health food preparations to lower cholesterol (such as red yeast rice, fish oil, omega 3 fatty acid) * Have undergone LDL apheresis in the past 1 year * Have recently used steroids, cyclosporine or isotretinoin * Have recently used an immunosuppressive therapy * Have recently received treatment with another antibody medication * Are currently using medications injected into the skin , except for single injections (for example flu vaccines) or injections into muscles * Are currently on a prescription or over-the-counter medicine for weight loss or are on a very low carbohydrate diet

Locations (49)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Encino, California, United States

Lancaster, California, United States

Spring Valley, California, United States

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)

Least square (LS) Means was calculated using analysis of covariance (ANCOVA) adjusted for disease classification, statin dose, baseline LDL-C measurement. Percent change from baseline response is the dependent variable.

Time frame: Baseline, Week 16

Secondary Outcomes

Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C

LS Mean was calculated using mixed model repeated measures (MMRM) analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.

Time frame: Baseline, Week 16

Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B)

LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.

Time frame: Baseline, Week 16

Percentage Change From Baseline in Lipoprotein(a) [Lp(a)]

Data was log-transformed for MMRM analysis, with change from baseline as the dependent variable, and baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included as independent variables. Percentage change from baseline in the original scale was then back-calculated from the log-transformed MMRM analysis.

Time frame: Baseline, Week 16

Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP)

Time frame: Baseline, Week 16

Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies

Time frame: Baseline through Week 24

Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels

Time frame: Baseline, Week 16

Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels

Time frame: Baseline, Week 16

Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014

Time frame: Week 12-16 (Q4W) - Predose, Week 8-16 (Q8W) - Predose

Number of Participants With an Injection Site Reaction

Time frame: Baseline through Week 24