期刊
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
卷 5, 期 1, 页码 661-670出版社
WILEY
DOI: 10.1016/j.trci.2019.09.010
关键词
Clinical trial design; Delay of onset; Genetic risk for AD; Mild cognitive impairment due to AD; Time to event; Trial population enrichment
资金
- Takeda Development Center Americas, Inc., Deerfield, IL, USA
- Zinfandel Pharmaceuticals, Inc., Durham, NC, USA
Introduction: Alzheimer's disease (AD) is a continuum with neuropathologies manifesting years before clinical symptoms; thus, AD research is attempting to identify more disease-modifying approaches to test treatments administered before full disease expression. Designing such trials in cognitively normal elderly individuals poses unique challenges. Methods: The TOMMORROW study was a phase 3 double-blind, parallel-group study designed to support qualification of a novel genetic biomarker risk assignment algorithm (BRAA) and to assess efficacy and safety of low-dose pioglitazone to delay onset of mild cognitive impairment due to AD. Eligible participants were stratified based on the BRAA (using TOMM40 rs 10524523 genotype, Apolipoprotein E genotype, and age), with high-risk individuals receiving low-dose pioglitazone or placebo and low-risk individuals receiving placebo. The primary endpoint was time to the event of mild cognitive impairment due to AD. The primary objectives were to compare the primary endpoint between high- and low-risk placebo groups (for BRAA qualification) and between high-risk pioglitazone and high-risk placebo groups (for pioglitazone efficacy). Approximately 300 individuals were also asked to participate in a volumetric magnetic resonance imaging substudy at selected sites. Results: The focus of this paper is on the design of the study; study results will be presented in a separate paper. Discussion: The design of the TOMMORROW study addressed many key challenges to conducting a dual-objective phase 3 pivotal AD clinical trial in presymptomatic individuals. Experiences from planning and executing the TOMMORROW study may benefit future AD prevention/delay-of-onset trials. (C) 2019 The Authors. Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据