Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and Safety of LIB003, Evolocumab and Alirocumab in CVD Patients, or at High Risk for CVD, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction (LIBerate-H2H)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 204
- 试验地点
- 6
- 主要终点
- LDL-C reduction from baseline at 12 weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
lipid levels measured and central laboratory will be blinded to participants, investigators, and sponsor, DSMB and CEC (Cardiovascular Events Committee)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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;
结局指标
主要结局
LDL-C reduction from baseline at 12 weeks
时间窗: 12 weeks
LS Mean percent change from baseline to week 12
次要结局
- Achieved ESC/EAS LDL-C goals(12 weeks)
- tolerability and safety of each treatment: injection site reactions(12 weeks)