Sample Collection and Analysis to Support the Qualification Plan for Drug Induced Skeletal Muscle Injury Biomarker Panel for DDT-BMQ-000081.

摘要 这个项目旨在增加我们对拟议的四个项目的敏感性的了解 检测药物所致骨骼肌损伤(DIMI)的骨骼肌损伤生物标志物 将解决药物开发中未得到满足的检测和监测DIMI的需求。这个 本项目产生的证据是支持四具骨骼的资格所必需的 肌肉特异性蛋白(骨骼肌钙蛋白I(TNNI2)、肌球蛋白轻链3(MYL3))。脂肪酸 结合蛋白3(FABP3)和肌酸激酶MM(CKM)作为骨骼肌生物标志物 美国食品和药物管理局(FDA)生物标志物资格认证计划造成的伤害 (BQP)。这项鉴定工作是由预测性安全测试联盟领导的 骨骼肌损伤工作组，这四个生物标志物对其来说是安全的 用于检测DIMI的生物标记物被接受为生物标记物资格认证计划。按顺序 为了进入下一阶段的资格赛，骨骼肌损伤工作组必须 准备一份资质计划，总结这四种生物标记物在 学习阶段研究并提出验证性研究，以支持拟议的 生物标志物资格认证计划正在考虑的使用情况。到目前为止， 骨骼肌损伤工作组在DIMI或肌肉损伤方面的临床数据有限 人口。为了解决这一差距，关键路径研究所(C-PATH)提出了以下建议 研究目的。具体目标1将进行一项研究，以确定拟议的 药物诱导的肌肉损伤生物标志物(TNNI2、MYL3、FABP3和CKM)。这项研究将 在密歇根大学医院收集125名受试者的单一样本 判定由DIMI、骨骼肌损伤或骨骼肌引起的骨骼肌损伤 健康受试者125例。这项研究将支持今后提交的 DDT#DDTBMQ000081的合格计划，通过定义建议的 肌肉损伤患者的药物性肌肉损伤生物标志物。

ABSTRACT This project seeks to increase our understanding of the sensitivity of the four proposed skeletal muscle injury biomarkers to detect drug-induced skeletal muscle injury (DIMI), which will address an unmet need in drug development for detecting and monitoring DIMI. The evidence generated by this project is necessary to support the qualification of four skeletal muscle specific proteins (skeletal troponin I (TNNI2), myosin light chain 3 (MYL3). Fatty acid binding protein 3 (FABP3), and creatine kinase MM (CKM)) as biomarkers of skeletal muscle injury by the Food and Drug Administration’s (FDA’s) Biomarker Qualification Program (BQP). This qualification effort is being led by the Predictive Safety Testing Consortium’s Skeletal Muscle Injury Working Group, for which these four biomarkers serve as safety biomarkers to detect DIMI was accepted into the Biomarker Qualification Program. In order to progress to the next stage of qualification, the Skeletal Muscle Injury Working Group must prepare a Qualification Plan which summarizes the performance of these four biomarkers in the learning phase studies and proposes the confirmatory studies to support the proposed context of use under consideration by the Biomarker Qualification Program. To date, the Skeletal Muscle Injury Working Group has limited clinical data in DIMI or muscle injury populations. To address this gap, the Critical Path Institute (C-Path) proposes the following research aim. Specific Aim 1 will conduct a study to determine the sensitivity of the proposed drug-induced muscle injury biomarkers (TNNI2, MYL3, FABP3, and CKM). The study will collect single samples from 125 subjects at the University of Michigan Hospital with adjudicated skeletal muscle injury due to DIMI, skeletal muscle injury, or skeletal muscle disease and 125 healthy subjects. This study will support the future submission of a Qualification Plan for DDT# DDTBMQ000081 by defining the sensitivity of the proposed drug-induced muscle injury biomarkers in muscle injury patients.