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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 900
- 试验地点
- 6
- 主要终点
- LDL-C change compared to placebo
研究概览
简要总结
This study is to assess LDL-C reductions at Week 52 with monthly (Q4W [≤31 days]) dosing of LIB003 (lerodalcibep) 300 mg administered subcutaneously (SC) compared to placebo in patients with CVD, or at high risk for CVD, on a stable diet and oral LDL-C lowering drug therapy
详细描述
Randomized, double-blind, placebo-controlled, Phase 3 study of 52 weeks duration.
Patients who fulfill the inclusion and exclusion criteria will be enrolled at up to 65 sites in the United States, Canada, Europe, South Africa, Asia, Australasia, and the Middle East. Patients will be randomized in a 2:1 ratio to LIB003 or placebo. The total study duration will be up to 63 weeks which includes up to a Screening Period and 52 weeks of study drug treatment. Following randomization patients will be dosed and seen in the clinic Q4W (≤31 days).
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
participants, study staff, investigator and sponsor blinded to treatment and lipid levels
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
- •Provision of written and signed informed consent prior to any study-specific procedure;
- •Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2;
- •History of CVD, (including cerebrovascular or peripheral arterial disease) or very-high risk for CVD as defined in the 2019 ESC/EAS Guidelines or
- •High risk for CVD as defined in the 2019 ESC/EAS Guidelines
- •At Screening or post Washout/Stabilization, 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;
- •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
- •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;
- •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
- •Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of screening, apheresis within 2 months prior to randomization; received other investigational agent(s) such as PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months of the Screening Visit;
- •Documented history of HoFH defined clinically or genetically
- •History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator
- •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;
- •Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2
- •Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × the ULN as determined by central laboratory analysis at screening
- •Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism
- •Uncontrolled Type 1 or Type 2 DM, defined as FBS ≥200 mg/dL or HbA1C ≥9%;
- •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 prior to the Screening Visit;
- •Planned cardiac surgery or revascularization;
- •New York Heart Association class III-IV heart failure
研究组 & 干预措施
LIB003 (lerodalcibep)
300 mg subcutaneously monthly (Q4W)
干预措施: lerodalcibep (Drug)
Placebo
matching placebo subcutaneously monthly (Q4W)
干预措施: Placebo (Other)
结局指标
主要结局
LDL-C change compared to placebo
时间窗: 52 weeks
Percent change in LS mean from baseline compared to placebo in LDL-C level
mean LDL-C change at week 50 and 52
时间窗: 50 and 52 weeks
Percent change in LS mean from baseline compared to placebo in LDL-C level at Weeks 50 and 52
次要结局
- Change in Free PCSK9(52 weeks)
- Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 52 weeks(52 weeks)
- Percentage of patients achieving 2019 ESC/EAS LDL-C goals(52 weeks)