A Phase 3, Prospective, Multicenter, Open Label, 2-Part Study of the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of ALXN2060 in Japanese Participants With Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 12
- 主要终点
- Part A: Change From Baseline To Month 12 Of Treatment In Distance Walked During The Six-minute Walk Test (6MWT)
研究概览
简要总结
This prospective study is designed to evaluate the efficacy, safety, and tolerability of ALXN2060 (also known as AG10), as well as to establish its pharmacokinetic and pharmacodynamic profile in Japanese participants with symptomatic ATTR-CM administered on a background of stable heart failure therapy.
详细描述
Participants will receive ALXN2060 for 12 months (Part A). Following the last visit (Month 12) of Part A, participants will continue the study in Part B, which will last for an additional 18 months (30 months from Day 1), during which all participants will continue to receive oral treatment with ALXN2060. Following completion of Month 30 assessments in Part B, participants will be offered the opportunity to continue to receive ALXN2060 in the Extension Period, which will last until ALXN2060 is approved in Japan or for up to 24 additional months, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established diagnosis of ATTR-CM with either wild-type TTR or a variant TTR genotype.
- •History of heart failure evidenced by at least 1 prior hospitalization for heart failure or clinical evidence of heart failure without prior heart failure hospitalization manifested by signs or symptoms of volume overload or elevated pressures or heart failure symptoms that required or requires ongoing treatment with a diuretic.
- •New York Heart Association Class I-III symptoms due to ATTR-CM.
- •On stable doses of cardiovascular medical therapy.
- •Completed ≥ 150 meters on the 6MWT on 2 tests prior to Day
- •Left ventricular (LV) wall (interventricular septum or LV posterior wall) thickness ≥ 12 millimeters.
- •Biomarkers of myocardial wall stress: N-terminal pro-brain-type natriuretic pep (NT-proBNP) level ≥ 300 picograms/milliliter (pg/mL).
排除标准
- •Acute myocardial infarction, acute coronary syndrome or coronary revascularization, or experienced stroke or transient ischemic attack within 90 days prior to screening.
- •Hemodynamic instability at screening.
- •Likely to undergo heart transplantation within a year of screening.
- •Current treatment with marketed drug products and other investigational agents for the treatment of ATTR-CM.
- •Current treatment with calcium channel blockers with conduction system effects (for example, verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed.
- •Confirmed diagnosis of light-chain (AL) amyloidosis.
- •Biomarkers of myocardial wall stress: NT-ProBNP ≥ 8,500 pg/mL.
- •Measure of kidney function, estimated glomerular filtration rate by Modification of Diet in Renal Disease formula < 30 mL/minute/1.73 meters squared.
研究组 & 干预措施
ALXN2060
Participants will receive ALXN2060.
干预措施: ALXN2060 (Drug)
结局指标
主要结局
Part A: Change From Baseline To Month 12 Of Treatment In Distance Walked During The Six-minute Walk Test (6MWT)
时间窗: Baseline, Month 12
The 6MWT measures how far a participant can walk in 6 minutes. Change from baseline was calculated as the difference between the distance walked during the 6MWT at 12 months and the distance walked during the 6MWT at baseline. To determine the baseline, at least 2 6MWTs were conducted \> 24 hours to ≤ 3 weeks apart prior to the first dose of ALXN2060. The baseline 6MWT is the average of the total distance walked by participants for the 2 qualifying 6MWTs that met all the protocol-defined criteria. Least squares mean change from baseline data were adjusted for baseline measures and visits.
Parts A and B: Number of Cardiovascular (CV)-Related Hospitalizations Over A 30-month Period
时间窗: 30 months
CV-related hospitalization was defined as the mean number of CV-related hospitalizations per participant per year over a 30-month period. CV-related hospitalizations were also reported as adverse events and were reviewed and adjudicated by an independent Clinical Events Committee (CEC).
All-cause Mortality (ACM) Over A 30-month Period
时间窗: 30 months
ACM was assessed as time from the date of first initiation of study treatment to the date of death during a 30-month period, and was analyzed using Kaplan-Meier analysis. Data are reported for the number of participants with ACM over the 30-month period.
次要结局
- Parts A and B: Change From Baseline In Distance Walked During The 6MWT(Baseline, Months 6, 9, 18, 24 and 30)
- Parts A and B: Change From Baseline In The Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)(Baseline, Months 6, 9, 12, 18, 24 and 30)
- Parts A and B: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation(Up to Month 30)
- Parts A and B: Change From Baseline In Serum Transthyretin (TTR) Concentration(Baseline, pre-dose on Days 14, 28 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30)
- Parts A and B: Change From Baseline In TTR Stabilization(Baseline, Pre-dose Days 14, 28 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30)