Trial to Evaluate Efficacy and Safety of LIB003, Evolocumab and Alirocumab in High-risk CVD Patients
Trial to Evaluate Efficacy and Safety of LIB003, Evolocumab and Alirocumab in High-risk CVD Patients
Comparison of LDL-C reductions at Week 12 of monthly (Q4W[≤ 31 days]) dosing of LIB003 300 mg
 administered subcutaneously (SC) to Q4W dosing of evolocumab (Repatha) 420 mg and alirocumab
 (Praluent) 300 mg in patients with CVD or at high risk for CVD on a stable diet and high
 intensity statin and other LDL-C-lowering drug therapy.
This is a randomized, open-label Phase 3 study of 12 weeks duration comparing Q4W SC doses of
 LIB003 300 mg, evolocumab (Repatha) 420 mg and alirocumab (Praluent) 300 mg. Approximately
 220 males and females aged ≥18 years who fulfill all of the inclusion and exclusion criteria
 will be enrolled at up to 25 sites in the United States. Patients will be stratified by
 baseline LDL-C and randomized in a 2:2:1 ratio to LIB003 (88 patients), Repatha (88 patients)
 or Praluent (44 patients) administered SC Q4W (≤31 days). The study will consist of a
 Screening Period and a Treatment Period. The total study duration will be up to 21 weeks
 which includes up to 9-week Screening Period (depending on period required for washout of
 PCSK9 mAb and/or intensification of statin treatment) and 12 weeks of study drug treatment.
Inclusion Criteria:

 -  signed informed consent

 -  diagnosed with CVD or a high risk of CVD based on 2019 ESC/EAS guidelines

 -  Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2

 -  LDL-C ≥90 mg/dL and TG ≤400 mg/dL while on stable diet & lipid-lowering oral drug
 therapy (ie, high intensity statin with or without ezetimibe) and no PCSK9 mAb for 4
 weeks if previously on Q2W dosing or 8 weeks if on Q4W dosing.

 -  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:

 -  at screening visit: not on high intensity statin; mipomersen or lomitapide within 6
 months; gemfibrozil within 6 weeks; bempedoic acid within 4 weeks; inclisiran within
 12 months; apheresis within 8 weeks

 -  HoFH defined clinically and/or genetically

 -  History of prior or active clinical condition or acute and/or unstable systemic
 disease compromising patient inclusion, at the discretion of the Investigator

 -  estimated glomerular filtration rate <30 mL/min/1.73m2 at screening

 -  Active liver disease or hepatic dysfunction, history of liver transplant, and/or AST
 or ALT >2.5 × the ULN

 -  Uncontrolled Type 1 or Type 2 diabetes mellitus, defined as fasting glucose ≥200 mg/dL
 or glycated hemoglobin (HbA1c) of ≥9%

 -  NY Heart Association class III-IV heart failure; or patients with last documented left
 ventricular ejection fraction <30%; planned PCI, CABG or cardiac surgery

 -  Uncontrolled hypertension defined as evidenced by a reproducible (repeated 5 minutes
 apart) sitting blood pressure ≥160 mmHg systolic or ≥100 mmHg diastolic;

 -  Enrolled in another investigational device or drug study, or less than 30 days or 5
 half-lives since ending another investigational device or drug study(ies), or
 receiving PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months
 of the Screening Visit;

 -  Have any other finding which, in the opinion of the Investigator, would compromise the
 patient's safety or participation in the study;