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

样品采集和分析以支持 DDT-BMQ-000081 药物引起的骨骼肌损伤生物标志物小组的资格计划。

• 批准号: 10411471
• 负责人: Nicholas King
• 金额: $ 24.98万
• 依托单位: CRITICAL PATH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10411471
• 关键词: Sample; Collection; Analysis; Support; Qualification

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.

摘要 本项目旨在增加我们对四个建议的敏感性的理解， 骨骼肌损伤生物标志物检测药物诱导的骨骼肌损伤（DIMI）， 将解决药物开发中检测和监测DIMI的未满足需求。的 该项目产生的证据是必要的，以支持四个骨骼的资格， 肌肉特异性蛋白质（骨骼肌钙蛋白I（TNNI 2）、肌球蛋白轻链3（MYL 3）。脂肪酸 结合蛋白3（FABP 3）和肌酸激酶MM（CKM））作为骨骼肌的生物标志物 美国食品药品监督管理局（FDA）生物标志物鉴定项目 （BQP）。这项鉴定工作由预测安全测试联盟领导， 骨骼肌损伤工作组，其中这四个生物标志物作为安全性 检测DIMI的生物标志物被接受进入生物标志物鉴定程序。为了 为了进入下一阶段的资格，骨骼肌损伤工作组必须 准备一份鉴定计划，总结这四种生物标志物的性能， 学习阶段研究并提出验证性研究，以支持拟议的 生物标志物鉴定计划正在考虑的使用背景。迄今为止 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。为了弥补这一差距，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（TNNI 2、MYL 3、FABP 3和CKM）。这项研究将 从密歇根大学医院的125名受试者中收集单一样本， 由于DIMI、骨骼肌损伤或骨骼肌损伤而判定的骨骼肌损伤 125名健康人和125名健康人。这项研究将支持今后提交一份 滴滴涕#DDTBMQ 000081的确认计划，通过定义拟定的 肌肉损伤患者中药物诱导的肌肉损伤生物标志物。