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

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

Eligibility

Inclusion Criteria

1. Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2;
2. History of CVD, (including cerebrovascular or peripheral arterial disease) or very-high risk for CVD as defined in the 2019 ESC/EAS Guidelines or
3. High risk for CVD as defined in the 2019 ESC/EAS Guidelines
4. 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;
5. 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
6. 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;
7. Females of childbearing potential must be using a highly effective form of birth control if sexually active

Exclusion Criteria

1. Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months, gemfibrozil within 6 weeks, apheresis within 2 months;
2. Received other investigational agent(s) such as PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months;
3. Documented history of HoFH defined clinically or genetically
4. History of any prior or active clinical condition or acute and/or unstable systemic disease
5. Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding;
6. Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2
7. Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × the ULN
8. Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism
9. Uncontrolled Type 1 or Type 2 DM, defined as FBS ≥200 mg/dL or HbA1C ≥9%;
10. 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;
11. Planned cardiac surgery or revascularization;
12. New York Heart Association class III-IV heart failure