Vucic Steve, Ryder Julie, Mekhael Linda, Rd Henderson, Mathers Susan, Needham Merilee, Dw Schultz, Mc Kiernan
Department of neurology, Westmead Hospital.
Westmead Clinical School University of Sydney, Sydney.
Medicine (Baltimore). 2020 Feb;99(6):e18904. doi: 10.1097/MD.0000000000018904.
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder of the human motor system. Neuroinflammation appears to be an important modulator of disease progression in ALS. Specifically, reduction of regulatory T cell (Treg) levels, along with an increase in pro-inflammatory effector T cells, macrophage activation and upregulation of co-stimulatory pathways have all been associated with a rapid disease course in ALS. Autologous infusion of expanded Tregs into sporadic ALS patients, resulted in greater suppressive function, slowing of disease progression and stabilization of respiratory function. Tecfidera (dimethyl fumarate) increases the ratio of anti-inflammatory (Treg) to proinflammatory T-cells in patients with relapsing remitting multiple sclerosis and rebalances the regulatory: inflammatory axis towards a neuroprotective phenotype. Consequently, the aim of this study was to assess the efficacy, safety, and tolerability of Tecfidera in sporadic ALS.
The study is an investigator led Phase 2 multi-center, randomized, placebo controlled, double blind clinical trial assessing the efficacy and safety of Tecfidera in patients with sporadic ALS. The study duration is 40 weeks, with a 36-week study period and end of study visit occurring at 40 weeks or at early termination/withdrawal from study. The TEALS study has been registered with the Australian and New Zealand Clinical Trials registry (ANZCTR) under the trials registration number ACTRN12618000534280 and has been approved by the Human Research Ethics Committee and Research Governance Office at the lead site (Westmead Hospital) with the ethics number HREC/17/WMEAD/353. The participating sites have obtained site specific ethics and governance approvals from the local institution.
The primary endpoint is slowing of disease progression as reflected by the differences in the ALS Functional Rating Score-Revised (ALSFRS-R) score at Week 36. The secondary endpoints will include effects in survival, lower motor neuron function, respiratory function, quality of life and safety.
This Phase 2 multi-center, randomized, placebo controlled, double blind clinical trial will provide evidence of efficacy and safety of Tecfidera in sporadic ALS.
肌萎缩侧索硬化症（ALS）是一种人类运动系统的进行性致命神经退行性疾病。神经炎症似乎是ALS疾病进展的重要调节因素。具体而言，调节性T细胞（Treg）水平降低，促炎效应T细胞增加、巨噬细胞活化以及共刺激途径上调均与ALS的快速病程相关。将扩增的Treg自体输注到散发性ALS患者体内，可产生更强的抑制功能，减缓疾病进展并稳定呼吸功能。富马酸二甲酯（Tecfidera）可增加复发缓解型多发性硬化症患者中抗炎（Treg）与促炎T细胞的比例，并使调节：炎症轴重新平衡至神经保护表型。因此，本研究的目的是评估Tecfidera在散发性ALS中的疗效、安全性和耐受性。
本研究是一项由研究者主导的2期多中心、随机、安慰剂对照、双盲临床试验，旨在评估Tecfidera在散发性ALS患者中的疗效和安全性。研究持续时间为40周，其中36周为研究期，研究结束访视在第40周或提前终止/退出研究时进行。TEALS研究已在澳大利亚和新西兰临床试验注册中心（ANZCTR）注册，试验注册号为ACTRN12618000534280，并已获得牵头研究点（韦斯特米德医院）的人类研究伦理委员会和研究管理办公室批准，伦理编号为HREC/17/WMEAD/353。参与研究的各研究点已获得当地机构的特定研究点伦理和管理批准。
主要终点是疾病进展减缓，以第36周时修订的ALS功能评定量表（ALSFRS-R）评分差异为依据。次要终点将包括对生存、下运动神经元功能、呼吸功能、生活质量和安全性的影响。
这项2期多中心、随机、安慰剂对照、双盲临床试验将为Tecfidera在散发性ALS中的疗效和安全性提供证据。
