A Study of LY3015014 in Participants With High Cholesterol

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Placebo; Drug: LY3015014; Drug: Statin; Drug: Ezetimibe

• Registration Number: NCT01890967
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-06-27
• Study First Submitted QC: 2013-06-27
• Study First Posted: 2013-07-02
• Primary Completion: 2014-04
• Study Completion: 2014-06
• Disposition First Submitted: 2014-09-29
• Disposition First Submitted QC: 2014-09-29
• Disposition First Posted: 2014-10-08
• Results First Submitted: 2017-05-25
• Results First Submitted QC: 2017-05-25
• Results First Posted: 2017-06-21
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-09
• Last Update Posted: 2019-09-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 527

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Q4W	Placebo	Placebo given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
20 mg LY3015014 Q4W	LY3015014	20 milligrams (mg) LY3015014 given subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
300 mg LY3015014 Q8W	LY3015014	300 mg LY3015014 given SC Q8W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
20 mg LY3015014 Q4W	Statin	20 milligrams (mg) LY3015014 given subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
120 mg LY3015014 Q4W	LY3015014	120 mg LY3015014 given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
120 mg LY3015014 Q4W	Statin	120 mg LY3015014 given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
300 mg LY3015014 Q4W	Statin	300 mg LY3015014 given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
100 mg LY3015014 Q8W	Statin	100 mg LY3015014 given SC once every 8 weeks (Q8W) for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
Placebo Q4W	Statin	Placebo given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
300 mg LY3015014 Q4W	LY3015014	300 mg LY3015014 given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
100 mg LY3015014 Q8W	LY3015014	100 mg LY3015014 given SC once every 8 weeks (Q8W) for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
300 mg LY3015014 Q8W	Statin	300 mg LY3015014 given SC Q8W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
20 mg LY3015014 Q4W	Ezetimibe	20 milligrams (mg) LY3015014 given subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
120 mg LY3015014 Q4W	Ezetimibe	120 mg LY3015014 given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
300 mg LY3015014 Q4W	Ezetimibe	300 mg LY3015014 given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
100 mg LY3015014 Q8W	Ezetimibe	100 mg LY3015014 given SC once every 8 weeks (Q8W) for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
300 mg LY3015014 Q8W	Ezetimibe	300 mg LY3015014 given SC Q8W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.
Placebo Q4W	Ezetimibe	Placebo given SC Q4W for 16 weeks. Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)	Baseline, Week 16	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.

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels	Baseline, Week 16	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.
Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014	Week 12-16 (Q4W) - Predose, Week 8-16 (Q8W) - Predose
Number of Participants With an Injection Site Reaction	Baseline through Week 24
Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C	Baseline, Week 16	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.
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP)	Baseline, Week 16	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.
Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B)	Baseline, Week 16	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.
Percentage Change From Baseline in Lipoprotein(a) [Lp(a)]	Baseline, Week 16	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.
Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies	Baseline through Week 24
Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels	Baseline, Week 16	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.

Trial Locations

Locations (1)

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.; 🇵🇷 Ponce, Puerto Rico