Study of Long-Term Efficacy and Safety of LIB003 in CVD or High Risk for CVD Patients Needing Further LDL-C Reduction

Study Overview
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Brief Summary
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This study is to assess LDL-C reductions at Week 52 with monthly (Q4W [≤31 days]) dosing of LIB003 (lerodalcibep) 300 mg administered subcutaneously (SC) compared to placebo in patients with CVD, or at high risk for CVD, on a stable diet and oral LDL-C lowering drug therapy

Detailed Description
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Randomized, double-blind, placebo-controlled, Phase 3 study of 52 weeks duration. Patients who fulfill the inclusion and exclusion criteria will be enrolled at up to 65 sites in the United States, Canada, Europe, South Africa, Asia, Australasia, and the Middle East. Patients will be randomized in a 2:1 ratio to LIB003 or placebo. The total study duration will be up to 63 weeks which includes up to a Screening Period and 52 weeks of study drug treatment. Following randomization patients will be dosed and seen in the clinic Q4W (≤31 days).

Official Title
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Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Patients With Cardiovascular Disease, or at High Risk for Cardiovascular Disease, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction

Conditions
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Cardiovascular Risk Factor, Cardiovascular Diseases, Cardiovascular Stroke, Hypercholesterolemia

Intervention / Treatment
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* Drug: lerodalcibep
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written and signed informed consent prior to any study-specific procedure; Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2; History of CVD, (including cerebrovascular or peripheral arterial disease) or very-high risk for CVD as defined in the 2019 ESC/EAS Guidelines or High risk for CVD as defined in the 2019 ESC/EAS Guidelines At Screening or post Washout/Stabilization, LDL-C ≥70 mg/dL and TG ≤400 mg/dL while on stable lipid-lowering oral drug therapy (i.e., maximally tolerated statin with or without ezetimibe); Patients unable to tolerate approved doses of a statin may take lower than approved doses and dose less frequently than daily as long as the dose and dosing frequency is consistent; Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, may also participate; Stable diet and lipid-lowering oral therapies (such as statins, ezetimibe, bile-acid sequestrants, OM-3 compounds, fenofibrate, bezafibrate, nicotinic acid, and bempedoic acid) or combinations thereof for at least 4 weeks Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥4 weeks after the last dose; for those on 300 mg or 420 mg Q4W (≤31 days) the washout period is ≥8 weeks following last dose; Females of childbearing potential must be using a highly effective form of birth control if sexually active and have a negative urine pregnancy test at the last Screening Visit; Exclusion Criteria: Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of screening, apheresis within 2 months prior to randomization; received other investigational agent(s) such as PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months of the Screening Visit; Documented history of HoFH defined clinically or genetically History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit; Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2 Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × the ULN as determined by central laboratory analysis at screening Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism Uncontrolled Type 1 or Type 2 DM, defined as FBS ≥200 mg/dL or HbA1C ≥9%; Uncontrolled serious cardiac arrhythmia, MI, unstable angina, PCI, CABG, placement of implantable cardioverter defibrillator or biventricular pacemaker, aortic valve surgery, or stroke within 3 months prior to the Screening Visit; Planned cardiac surgery or revascularization; New York Heart Association class III-IV heart failure

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: Placebo-controlled, randomized 2:1 to Active or placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIB003 (lerodalcibep)<br>300 mg subcutaneously monthly (Q4W) | Drug: lerodalcibep<br>* 300 mg subcutaneous injection every month (Q4W)<br>* Other names: LIB003;|
| Placebo Comparator: Placebo<br>matching placebo subcutaneously monthly (Q4W) | Other: Placebo<br>* matching subcutaneous injection every month (Q4W)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C change compared to placebo | Percent change in LS mean from baseline compared to placebo in LDL-C level | 52 weeks | 
| mean LDL-C change at week 50 and 52 | Percent change in LS mean from baseline compared to placebo in LDL-C level at Weeks 50 and 52 | 50 and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 52 weeks | Evaluation of Adverse Events based on MedRA based on ITT population | 52 weeks | 
| Change in Free PCSK9 | Percent change in LS mean from baseline compared to placebo in free PCSK9 | 52 weeks | 
| Percentage of patients achieving 2019 ESC/EAS LDL-C goals | To assess the effects of LIB003 on the percentage of patients achieving an LDL-C <40 mg/dL, 55 mg/dL, <70 mg/dL, and 100 mg/dL | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lerodalcibep, PCSK9 inhibitor