Study to Evaluate the Long-Term Efficacy and Safety of the Investigational Drug LIB003 for the Reduction of Cholesterol in Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease.
- Conditions
- Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease, on Stable Lipid-Lowering Therapy Requiring Additional Low-Density Lipoprotein Cholesterol ReductionMedDRA version: 20.1Level: LLTClassification code 10007648Term: Cardiovascular disease, unspecifiedSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2020-004393-22-NO
- Lead Sponsor
- IB Therapeutics, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 900
1. Provision of written and signed informed consent prior to any study-specific procedure;
2. Male or female, =18 years of age at the first Screening Visit;
3. Weight of =40 kg (88 lb) and body mass index (BMI) =17 and =42 kg/m2;
4. Evidence of very-high or high risk for CVD:
o Very-high risk for CVD including history of stable CVD, defined as previous myocardial infarction (MI) (ST-elevation MI or non-ST-elevation MI), angioplasty, documented coronary artery disease (stress echo, computed tomography [CT], coronary angiography, or invasive angiography) or cerebrovascular or peripheral arterial disease without a recent event (eg, acute coronary syndrome, unstable angina, coronary artery bypass grafting, percutaneous coronary intervention, stroke, MI, carotid endarterectomy) within 3 months prior to screening;
OR
o High risk for CVD (ASCVD risk equivalent) including type 2 diabetes mellitus, FH, untreated LDL-C >190 mg/dL, or a 10-year risk of a CVE of =10% as assessed by Risk Score for Cardiovascular Disease or equivalent;
o Note: ASCVD encompasses acute coronary syndrome, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, and peripheral arterial disease, including aortic aneurysm, all of atherosclerotic origin.
o Note: Definite, probable, or possible FH by Simon Broome Register Criteria or Dutch Lipid Clinic Network Criteria
5. At the defined eligibility visit (screening or post washout/stabilization), a calculated LDL-C (by Friedewald formula) =70 mg/dL (if very-high risk for CVD) or =100 mg/dL (if high risk or no CVD) and TG =400 mg/dL while on stable lipid-lowering oral drug therapy (ie, maximally tolerated statin with or without ezetimibe);
o Note: Patients unable to tolerate approved doses of a statin may take lower than approved doses and less frequently than daily as long as the dose and dosing frequency are consistent.
o Note: Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, and unable to tolerate any other allowed oral lipid-lowering agent, and thus on no lipid-lowering therapy may also participate.
6. On a stable diet and lipid-lowering oral therapy (statins, ezetimibe, bile-acid sequestrants, OM-3 compounds, fenofibrate, bezafibrate, nicotinic acid, and bempedoic acid) or combinations thereof, for at least 4 weeks (excluded oral lipid-lowering agents including mipomersen, lomitapide, and gemfibrozil);
7. 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 a dose of 300 mg or 420 mg Q4W (=31 days) the washout period is =8 weeks following the last dose. For patients who have received an siRNA PCSK9 inhibitor the washout period is =360 days post last dose;
8. 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;
o Note: Highly effective methods of birth control include refraining from heterosexual sexual intercourse during the entire period of risk, birth control pills or patches, intrauterine devices (IUDs), sexual activity with a male partner who has had a vasectomy, condom or diaphragm or cervical cap with spermicide or IUD, oral, implantable, or injectable contraceptives. Menopause is defined as 12 months of spontaneous and continuous amenorrhea in a female =55 years old or 12 months of spontaneous and cont
1. Use of prohibited oral lipid-lowering agents, including mipomersen or lomitapide within 6 months of screening, or gemfibrozil within 6 weeks of screening;
2. Low-density lipoprotein or plasma apheresis within 2 months prior to randomization;
3. Documented history of HoFH defined as clinical and/or genetic with true HoFH (ie, identical pathogenic variants) or compound heterozygous (ie, 2 different pathogenic LDLR variants) or combined heterozygous (2 different pathogenic FH variants such as LDLR plus apo B, or LDLR plus PCSK9 GOF) mutation;
4. History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator, including but not limited to clinically significant pulmonary, hematologic, gastrointestinal, endocrine (excluding diabetes), immunologic, dermatologic, neurologic, or psychiatric disease, which in the Investigator’s opinion would not be suitable for the study from a patient safety consideration or could interfere with the results of the study;
5. 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;
Note: Highly effective methods of birth control include refraining from heterosexual sexual intercourse during the entire period of risk, birth control pills or patches, IUDs, sexual activity with a male partner who has had a vasectomy, condom or diaphragm or cervical cap with spermicide or IUD, oral, implantable, or injectable contraceptives.
6. Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2 at the Screening Visit;
7. Active liver disease or hepatic dysfunction (eg, cirrhosis, alcoholic liver disease, known hepatitis B [HBV] or hepatitis C [HCV], autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, and/or AST or ALT >2.5 × the ULN as determined by central laboratory analysis at screening (tests that result in ALT or AST up to 3 × ULN may have 1 repeat test to confirm eligibility during the Screening Period);
8. Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by thyroid-stimulating hormone (TSH) below the lower limit of normal or >1.5 × ULN, respectively, at the Screening Visit. If TSH is above/below these cut points, patients can enter if free triiodothyronine (FT3) is within the reference range. If controlled, treatment should be stable for at least 3 months prior to the Screening Visit;
9. Uncontrolled type 1 or type 2 diabetes mellitus, defined as fasting glucose =200 mg/dL or glycated hemoglobin (HbA1c) of >9%;
10. Uncontrolled serious cardiac arrhythmia (sustained ventricular tachycardia, frequent non-sustained ventricular tachycardia, any ventricular fibrillation episode, wide-complex tachycardia, atrial fibrillation with rapid ventricular response, and severe second degree or third degree atrioventricular block), MI, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, placement of implantable cardioverter defibrillator or biventricular pacemaker, aortic valve surgery, or stroke within 3 months prior to the Screening Visit;
11. Planned cardiac surgery or revascularization;
12. New York Heart Association class III-IV heart failure; or patients with last documented left ventricular ejection fraction <30% by stand
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method