Study to Evaluate Efficacy and Safety of LIB003 in Patients on Lipid-Lowering Therapy Needing Additional LDL-C Reduction

Study Overview
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Brief Summary
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Study to assess the LDL-C lowering efficacy of different doses of LIB003 administered every 4 weeks in subjects on stable statin and/or ezetimibe therapy

Detailed Description
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Randomized, Double-Blind, Placebo-Controlled, Phase 2 study to assess the LDL-C lowering efficacy at Week 12 of various doses of LIB003 administered subcutaneously (SC) every 4 weeks (Q4W) in patients with hypercholesterolemia on stable diet and oral LDL-C-lowering drug therapy.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Phase 2, Dose Finding Study to Evaluate the Efficacy and Safety of LIB003 in Patients on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction

Conditions
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LDL Cholesterol

Intervention / Treatment
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* Biological: LIB003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years of age or older Elevated LDL-C on current lipid lowering therapy and; prior atherosclerotic cardiovascular disease (ASCVD) event or evidence of ASCVD or without ASCVD but at high risk for ASCVD based on AHA/ACC CVD risk calculator, or aged 40 years and older with diabetes and moderate- to high-intensity statin, or pre-treatment LDL-C 190 mg/dL or greater or heterozygous familial hypercholesterolemia (HeFH) Body mass index (BMI) between 18 and 40 kg/m2 Exclusion Criteria: Females of childbearing potential not using or willing to use an effective form of contraception, or pregnant or breastfeeding, or who have a positive serum pregnancy test at screening Homozygous familial hypercholesterolemia LDL or plasma apheresis within 2 months; lomitapide or mipomersen within 12 months Uncontrolled cardiac arrhythmia, myocardial infarction, unstable angina, PCI, CABG, or stroke within 3 months prior to enrollment Uncontrolled cardiac arrhythmia, myocardial infarction, unstable angina, PCI, CABG, or stroke within 3 months prior to enrollment Newly diagnosed or poorly controlled (HbA1c >9%) type 2 diabetes Uncontrolled hypertension Moderate to severe renal insufficiency Elevated liver function test at screening Uncontrolled cardiac arrhythmia or prolonged QT on EKG A history of prescription drug abuse, illicit drug use, or alcohol abuse

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
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled trial to evaluate LDL-C reduction with 3 different doses of LIB003 compared to placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIB003 150 mg or matching placebo<br>SC LIB003 150 mg or placebo every 4 weeks | Biological: LIB003<br>* LIB003 or placebo<br>|
| Experimental: LIB003 300 mg or matching placebo<br>SC LIB003 300 mg or placebo every 4 weeks | Biological: LIB003<br>* LIB003 or placebo<br>|
| Experimental: LIB003 350 mg or matching placebo<br>SC LIB003 350 mg or placebo every 4 weeks | Biological: LIB003<br>* LIB003 or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent reduction in Low Density Lipoprotein Cholesterol (LDL-C) at week 12 | Change in serum LDL-C from baseline after 12 weeks | baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of treatment emergent adverse events (TEAEs) | safety and tolerability will be based on the incidence and severity of treatment emergent adverse events | baseline to 12 weeks | 
| Percent reduction in apolipoprotein B (Apo B) at week 12 | Change in serum Apo B from baseline after 12 weeks | baseline to 12 weeks | 
| Percent reduction in lipoprotein (a) [Lp(a)] at week 12 | Change in serum Lp(a) from baseline after 12 weeks | baseline to 12 weeks | 
| Percent reduction in free PCSK9 at week 12 | Change in serum free PCSK9 from baseline after 12 weeks | baseline to 12 weeks | 
| Presence of anti LIB003 antibodies (ADAs) | Measurement of ADAs at baseline and various intervals | baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low density lipoprotein cholesterol, PCSK9