A MULTICENTER, INTERNATIONAL, PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF DAILY ORAL DOSING OF TAFAMIDIS MEGLUMINE (PF-06291826) 20 MG OR 80 MG IN COMPARISON TO PLACEBO IN SUBJECTS DIAGNOSED WITH TRANSTHYRETIN CARDIOMYOPATHY (TTR-CM)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 441
- 试验地点
- 80
- 主要终点
- Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations
研究概览
简要总结
This Phase 3 study will investigate the efficacy, safety and tolerability of an oral daily dose of 20 mg or 80 mg tafamidis meglumine capsules compared to placebo in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy.
详细描述
Phase 3, multicenter, global, three-arm, parallel design, placebo-controlled, double-blind, randomized study to determine efficacy, safety and tolerability of tafamidis on clinical outcomes (all-cause mortality and frequency of cardiovascular-related hospitalizations) in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy.
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)
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
- •Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement,
- •Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm,
- •Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or mass spectrometry
排除标准
- •A New York Heart Association (NYHA) classification of IV.
- •Presence of primary (light chain) amyloidosis.
- •Prior liver or heart transplantation or implanted cardiac mechanical assist device.
研究组 & 干预措施
Tafamidis - 20 mg
Active Treatment-Low dose
干预措施: Tafamidis (Drug)
Tafamidis - 80 mg
Active Treatment-High Dose
干预措施: Tafamidis (Drug)
Placebo
Placebo control
干预措施: Placebo (Drug)
结局指标
主要结局
Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations
时间窗: Baseline up to Month 30
All-cause mortality and frequency of cardiovascular hospitalization were analyzed using Finkelstein-Schoenfeld method. The method combines all-cause mortality and frequency of CV-related hospitalizations in a hierarchical fashion using all-cause mortality first. The method compares every participant with every other participant within strata, assigning a +1 to the "better" participant and a -1 to the "worse" participant and 0 if they are "tied". Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device, were handled in the same manner as death. 'Win' represents a participant doing better based on hierarchical comparison. The reported unit is the total "wins" for each treatment group from performing such a hierarchical comparison across all 4 strata in the study.
次要结局
- All-Cause Mortality(Baseline up to Month 30)
- Number of Participants With Cardiovascular-Related Mortality(Baseline up to Month 30)
- Percentage of Participants With Stabilized Transthyretin (TTR) at Month 1(Month 1)
- Frequency of Cardiovascular-Related Hospitalizations(Baseline to Month 30)
- Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at Month 30(Baseline, Month 30)
- Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 30(Baseline, Month 30)