背景:遗传性转甲状腺素蛋白(ATTRv)淀粉样变性是一种罕见的,严重,进步,衰弱,以及最终由甲状腺素运载蛋白(TTR)淀粉样原纤维的全身沉积引起的致命疾病。ATTRv淀粉样变性发生在男性和女性中。Eplontersen(ION-682884),设计用于降解肝脏TTRmRNA的配体缀合的反义寡核苷酸,正在评估ATTRv淀粉样变性多发性神经病(ATTRv-PN)的治疗方法,多中心,开放标签NEURO-TTRansform研究(NCT04136184)。为了描述这项关键试验的研究人群,在此,我们报告参加NEURO-TTRansform研究的患者的基线特征.
方法:符合NEURO-TTRansform诊断的患者年龄为18-82岁,诊断为ATTRv-PN和Coutinho1期(无辅助门诊)或2期(无辅助门诊)疾病;记录的TTR基因变异;与ATTRv相关的神经病的体征和症状;没有先前的肝移植;和纽约心脏协会(NYHA)功能I或II级。
结果:NEURO-TTRansform研究纳入了15个国家/地区的168名患者(北美,15.5%;欧洲,38.1%;南美/澳大利亚/亚洲,46.4%)。在基线,研究队列的平均年龄为52.8岁,69.0%的患者为男性,78.0%的患者为白人。V30M变异最为普遍(60.1%的患者),患病率因地区而异。总的来说,56.5%和17.3%的患者以前曾接受过tafamidis或diflunnisal的治疗,分别。大多数患者(79.2%)患有Coutinho1期疾病(步行无障碍)和早期(50岁之前)疾病发作(53.0%)。从诊断到登记的时间为46.6(57.4)个月(平均值[标准差])。大多数患者的基线多发性神经病障碍(PND)评分为I(40.5%)或II(41.1%),平均改良神经病变损伤评分+7(mNIS+7)为79.0。
结论:正在进行的NEURO-TTRansform研究中的招募人群具有当代临床实践的全球代表性特征。
背景:ClinicalTrials.gov标识符NCT04136184。
遗传性转甲状腺素蛋白淀粉样变性,也称为ATTRv淀粉样变性,是一种罕见且严重的疾病,在家庭中传播。患有ATTRv淀粉样变性的人有一种遗传变异,导致他们的肝脏产生异常版本的甲状腺素运载蛋白(也称为“TTR”),它们聚集在一起成为称为淀粉样蛋白的“簇”。淀粉样蛋白聚集在各种身体组织和器官中,例如肝脏,神经,心,和肾脏,造成损害,最终可能导致死亡。ATTRv淀粉样变性是一种进行性疾病,这意味着随着时间的推移,情况会变得更糟。传统上,肝移植是唯一的治疗选择。最近,靶向TTR的药物已被FDA批准,潜在的药物正在临床试验中进行测试。Eplontersen旨在降解肝脏中的TTRmRNA并抑制TTR蛋白的产生。NEURO-TTRansform是一项全球3期研究,旨在调查eplontersen在168例成人ATTRv淀粉样变性多发性神经病(ATTRv-PN)中的有效性和安全性。淀粉样蛋白在周围神经中积聚导致多系统损伤并最终死亡的疾病。这篇科学文章描述了登记时患者的特征,包括年龄,性别,地理位置,和疾病相关信息,以帮助提高对ATTRv-PN的理解。NEURO-TTRansform是一项正在进行的研究,结果将按照分析计划中的预定时间公布。
BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform
study (NCT04136184). To describe the
study population of this pivotal
trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform
study.
METHODS: Patients eligible for NEURO-TTRansform were 18-82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II.
RESULTS: The NEURO-TTRansform
study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the
study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0.
CONCLUSIONS: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice.
BACKGROUND: ClinicalTrials.gov identifier NCT04136184.
Hereditary transthyretin amyloidosis, also called ATTRv amyloidosis, is a rare and serious disease that is passed down within families. People with ATTRv amyloidosis have a genetic variant that causes their liver to make abnormal versions of the transthyretin protein (also known as “TTR”), which clump together into “clusters” called amyloids. The amyloid clusters build up in various body tissues and organs such as the liver, nerves, heart, and kidney, causing damage that could ultimately lead to death. ATTRv amyloidosis is a progressive disease, meaning that it gets worse over time. Liver transplant has traditionally been the only treatment option. Recently, drugs that target TTR have been approved by the FDA, and potential drugs are being tested in clinical trials. Eplontersen is designed to degrade TTR mRNA in the liver and inhibit the production of TTR protein. NEURO-TTRansform is a global phase 3 study investigating the effectiveness and safety of eplontersen in 168 adults with ATTRv amyloidosis with polyneuropathy (ATTRv-PN), a disease in which amyloid accumulation in peripheral nerves causes multisystem damage and eventually death. This scientific article describes the characteristics of the patients at enrollment, including age, gender, geographic location, and disease-related information, to help improve the understanding of ATTRv-PN. NEURO-TTRansform is an ongoing study, and the results will be published at a later time as prespecified in the analysis plan.