A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to evaLuate the effIcacy and Safety of abeLacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral antiCoagulation (LILAC-TIMI 76)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,500
- 试验地点
- 1,398
- 主要终点
- Safety: Time to first occurrence of Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding
研究概览
简要总结
A study to evaluate the effect of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism (SE) in patients with Atrial Fibrillation (AF) who have been deemed by their responsible physicians or by their own decision to be unsuitable for oral anticoagulation therapy.
详细描述
Patients enrolled in the study are randomized in a 1:1 ratio to receive abelacimab 150 mg SC or matching placebo once monthly. The study is comprised of 3 periods: 1) screening period of up to 60 days, 2) an event-driven, double-blind treatment period (abelacimab 150 mg SC or matching placebo) completed after at least 111 patients have experienced an adjudicated primary endpoint event, and 3) EoT visit in core part followed by either (i) a 30-day follow-up period (EoS for core part) OR (ii) an optional OLE beginning at the EoT visit for eligible patients to receive open-label abelacimab treatment. The optional extension will only be offered to patients following regulatory and ethics approval in participating countries.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is able to understand and has provided written informed consent to participate in the trial
- •Diagnosed Atrial Fibrillation (AF) or atrial flutter (documented on an electrocardiogram (ECG) or monitor recording)
- •Age 65-74 and a CHA2DS2VASc ≥4 OR age ≥75 and a CHA2DS2VASc ≥3
- •Patient is judged by the responsible physician to be unsuitable for oral anticoagulation because the risks outweigh the benefits or the patient is unwilling to take oral anticoagulation AND this determination was made prior to and independent of the study
- •At least 1 bleeding risk factor such as severe renal insufficiency, planned daily use of antiplatelet medication for the duration of the trial, history of bleeding from a critical area, or other conditions associated with increased risk of bleeding such as chronic nonsteroidal anti-inflammatory drug (NSAID) use, frailty or multiple falls
- •Patient is judged by the responsible physician to be unsuitable for left atrial appendage (LAA) closure or occlusion device, an approved device is not available, or the patient is unwilling to undergo the procedure AND this determination was made prior to and independent of the study
排除标准
- •AF due to an ongoing acute reversible cause (e.g., cardiac surgery, pulmonary embolism (PE), untreated hyperthyroidism, alcohol use)
- •Patients who within 60 days prior to randomization (1) received a vitamin K antagonists (VKA) (e.g., warfarin, phenprocoumon, acenocoumarol) or a direct oral anticoagulant (DOAC) such as, dabigatran, rivaroxaban, apixaban, or edoxaban or (2) were newly diagnosed with AF
- •Patients with an intracranial or intraocular bleed within the 3 months prior to screening or any history of spontaneous intracerebral hemorrhage at any time in the absence of antithrombotic treatment
- •Any stroke within 14 days before randomization or transient ischemic attack (TIA) within 3 days before randomization
- •Mechanical heart valve or valve disease that is expected to require mechanical valve replacement intervention (surgical or invasive) during the course of the study
- •Patients on dialysis at screening or who are planned to start dialysis within 6 months
- •Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Abelacimab (MAA868)
Patients will be randomized in a 1:1 ratio to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly.
干预措施: Abelacimab (Biological)
Placebo
Patients will be randomized in a 1:1 ratio to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety: Time to first occurrence of Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding
时间窗: Up to 30 months
Efficacy: Time to first event of ischemic stroke or systemic embolism (SE)
时间窗: Up to 30 months
Undetermined strokes will be counted as ischemic strokes
次要结局
- Efficacy: All-cause mortality(Up to 30 months)
- Efficacy: Cardiovascular (CV) mortality(Up to 30 months)
- Efficacy: Time to first event of ischemic stroke, systemic embolism (SE), or Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding event(Up to 30 months)
- Efficacy: Time to first event of ischemic stroke, systemic embolism (SE), myocardial infarctions (MI), venous thromboembolism (VTE), or acute limb ischemia(Up to 30 months)
- Time to first event of ischemic stroke, systemic embolism (SE), myocardial infarctions (MI), venous thromboembolism (VTE), acute limb ischemia, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding(Up to 30 months)