Trial to Evaluate Efficacy and Safety of LIB003 and Inclisiran in High-risk CVD Patients

Study Overview
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Brief Summary
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Comparison of LDL-C reductions of lerodalcibep (LIB003) 300 mg to inclisiran (Leqvio®) 284 in patients at very-high risk or high-risk for CVD on stable diet and oral LDL-C-lowering drug therapy

Detailed Description
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Randomized, Open Label (lipids blinded), Phase 3 Study to Evaluate the Efficacy and Safety of Lerodalcibep (LIB003) at Day 270 of subcutaneous (SC) monthly (QM [≤31 days]) lerodalcibep (LIB003) 300 mg administered to SC inclisiran (Leqvio®) 284 mg at Days 1 and 90 in patients with very-high risk or high-risk CVD or at high risk for CVD with LDL-C ≥85 mg/dL on a stable diet and oral LDL-C-lowering drug therapy

Official Title
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Randomized Open Label, Phase 3 Study to Compare the Efficacy and Safety of Lerodalcibep (LIB003) to Inclisiran in Patients at Very High or High Risk for CVD, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction

Conditions
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Hypercholesterolemia, Atherosclerotic Ischemic Disease

Intervention / Treatment
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* Biological: lerodalcibep
* Drug: Inclisiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed informed consent prior to any study-specific procedure; Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥16 and ≤42 kg/m2; Very- high or high risk for CVD as defined in 2019 ESC/EAS Guidelines High-intensity statin (daily atorvastatin 40/80 or rosuvastatin 20/40) without other acceptable oral lipid lowering treatment plus diet; stable >4 weeks with LDL-C ≥85 mg/dL and triglycerides ≤400 mg/dL Women of childbearing potential (WOCBP) must continue using a highly effective form of birth control if sexually active Males whose partners are of CBP and not using a highly effective form of birth control will either be surgically sterile or agree to use the following forms of contraception, male or female condom with spermicide Exclusion Criteria: Prior or active clinical condition or acute and/or unstable systemic disease, including cancer, compromising patient inclusion or preclude completion of the study, at the discretion of the Investigator Homozygous FH non-high intensity statins, mipomersen, lomitapide, gemfibrozil, and bempedoic acid PCSK9 mAb within 4 weeks of screening or siRNA within 1 year Severe renal dysfunction, defined eGFR <30 ml/min Recent, within 3 months of screening, atherosclerotic event or intervention planned cardiac procedure NYHA class III or IV heart failure active liver disease uncontrolled diabetes defined as fasting glucose >200 mg/dL and HbA1c > 9% uncontrolled BP ≥180 mmHg systolic or ≥110 mmHg diastolic;

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, comparative trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lerodalcibep<br>300 mg SC dosed monthly | Biological: lerodalcibep<br>* 300 mg<br>* Other names: LIB003;|
| Active Comparator: inclisiran<br>284 mg SC dosed Day 1 and Day 90 | Drug: Inclisiran<br>* 284 mg<br>* Other names: Leqvio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C change | Percent LDL-C change from baseline | Day 270 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | frequency and severity of injection site reactions (ISRs) | 270 days | 
| Serum free PCSK9 levels | Percent change in free PCSK9 from baseline | Day 270 | 
| Apolipoproteins | Percent change in Apo B and Lp(a) from baseline | Day 270 | 
| Treatment goal achievement | Percent of patients reaching ESC/EAS treatment goals | Day 270 | 

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