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

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

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

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

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;