NCT04136171已完成3 期
A Phase 3 Global, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,438
- 试验地点
- 284
- 主要终点
- Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140
研究概览
简要总结
To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care (SoC).
详细描述
This is a multicenter, double-blind study in 1438 participants, who will be randomized to receive subcutaneous (SC) injections of either eplontersen or placebo once every 4 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.
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
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method
- •Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
- •Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed
- •End-diastolic interventricular septum thickness of > 12 millimeters (mm) on Screening echocardiogram
- •New York Heart Association (NYHA) class I-III
排除标准
- •Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
- •Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
- •Monoclonal gammopathy of undetermined significance (MGUS) and/or alterations in immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy. For participants with chronic kidney disease (CKD) and without presence of monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26-2.
- •Results different from that may be discussed with local hematologist, Investigator and Medical Monitor if the risks associated with the biopsy outweigh the benefits
- •Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization
- •Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or ribonucleic acid (RNA) therapeutic (including small interfering ribonucleic acid [siRNA]; does not apply to COVID-19 mitochondrial [mRNA] vaccinations)
- •Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.
研究组 & 干预措施
Placebo
Placebo Comparator
Eplontersen-matching placebo by subcutaneous injection once every 4 weeks
干预措施: Placebo (Drug)
Eplontersen
Experimental
Eplontersen by subcutaneous injection once every 4 weeks
干预措施: Eplontersen (Drug)
结局指标
主要结局
Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140
时间窗: Baseline up to Week 140
次要结局
- Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 140(Baseline to Week 140)
- Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 140(Baseline to Week 140)
- Recurrent CV Clinical Events up to Week 140(Baseline up to Week 140)
- All-Cause Mortality up to Week 160(Baseline up to Week 160)
- All-Cause Mortality up to Week 140(Baseline up to Week 140)
- Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140 in Subgroup of Patients Treated with Tafamidis at Baseline(Baseline up to Week 140)
- CV Mortality up to Week 160(Baseline up to Week 160)
- CV Mortality up to Week 140(Baseline up to Week 140)
- Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 140(Baseline to Week 140)
- Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 140(Baseline to Week 140)
- Recurrent CV Clinical Events up to Week 140(Baseline up to Week 140)
- All-Cause Mortality up to Week 160(Baseline up to Week 160)
- All-Cause Mortality up to Week 140(Baseline up to Week 140)
- Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140 in Subgroup of Patients Treated with Tafamidis at Baseline(Baseline up to Week 140)
- CV Mortality up to Week 160(Baseline up to Week 160)
- CV Mortality up to Week 140(Baseline up to Week 140)
研究者
研究点 (284)
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