Fast Fail Trials in Autism Spectrum Disorders (FAST-AS)

自闭症谱系障碍的快速失败试验 (FAST-AS)

基本信息

批准号：
8947118
负责人：
JAMES T. MCCRACKEN
金额：
$ 609.24万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-05 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8947118
关键词：
Address Adolescent Adult Affect Agreement Area Award Basic Science Behavior Biological Biological Markers Businesses Calendar Categories Chemicals Child Clinical Clinical Research Clinical Trials Clinical Trials Design Communication Complex Consent Forms Contractor Contracts Contracts Review DSM-IV Data Development Diagnosis Diagnostic Dimensions Direct Costs Disclosure Disease Dose Drug Kinetics Electronic Mail Elements Ensure Evaluation Exclusion Exclusion Criteria FDA approved Frequencies Hour Human Human Resources Individual Institutional Review Boards Intellectual Property Intervention Investigational Drugs Judgment Lead Legal patent Length Marketing Measures Mediation Mental disorders Methods Minority Modification Molecular Molecular Target Monitor National Institute of Mental Health Neurodevelopmental Disorder Outcome Outcome Measure Pamphlets Pattern Pharmacologic Substance Pharmacological Treatment Phase Preparation Procedures Progress Reports Protocols documentation Psychopathology Public Health Randomized Reporting Research Research Design Risk Safety Sample Size Schedule Severities Site Stereotyping Stratification Structure Subjects Selections Support Contracts Telephone Testing Therapeutic United States National Institutes of Health Visit Woman Work autism spectrum disorder cohort cost data sharing dosage financial conflict of interest follow-up human data human subject protection inclusion criteria innovation interest material transfer agreement meetings novel preclinical study primary outcome prior authorization programs protocol development social social communication impairment symposium tool treatment duration

项目摘要

The outcome of the FAST-AS initiative is expected to lead to an enhanced understanding of underlying mechanisms and development of innovative pharmacological treatment approaches for Autism Spectrum Disorder (ASD). ASD is a group of complex neurodevelopmental disorders that range in severity and that are characterized by social impairments, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior. This initiative seeks to expeditiously test and analyze novel interventions (i.e., compounds) and their molecular and/or clinical targets for treating clinical dimensions of psychopathology (e.g., social engagement, rigidity or inflexibility) comprising the core features of ASD. Of particular interest are features of ASD as described in the current DSM-IV-TR diagnostic entities, but not typically identified as the primary target of current clinical therapeutics. As described above, there is interest in the study of mechanisms that cut across traditional disorder categories and where relevant mechanisms and clinical targets are assessed directly rather than being inferred through assignment of a particular diagnosis. The outcome of this initiative is expected to lead to enhanced understanding of specific target engagement by such novel interventions, leading to development of innovative treatment approaches for clinical dimensions of psychopathology associated with ASD. In this context, novel interventions (i.e., compounds) may refer either to new chemical entities (NCEs) or to compounds that are being considered for re-purposing from other indications. Testing of compounds that have been FDA-approved for other indications (re-purposing) is of interest if recent basic research discoveries suggest that the compound(s) have the potential to affect a biological mechanism contributing to mental disorders and that has previously been untested in clinical studies. Compounds acting on molecular targets that replicate those of currently marketed psychiatric pharmaceuticals are not of interest for this contract. The primary objectives of this contract are: A. To expeditiously perform small-scale Phase I and/or Phase IIa clinical trials (e.g., First In Human (FIH), Proof of Clinical Mechanism (POCM), Proof of Concept (POC)) to demonstrate target engagement, safety, and early signs of efficacy of such promising interventions in healthy child, adolescent, and/or adult subjects and/or a well-characterized cohort of children, adolescents, and/or adults with clinical dimensions of psychopathology associated with ASD. B. Depending on pilot data available for compounds selected for testing, each trial may be a single-site or multisite study with a number of subjects adequate to successfully address the primary aims (e.g., pharmacologic dose range, safety in humans, molecular and/or clinical target engagement, potential biomarkers, biological effects, early signs of efficacy) and inform a judgment whether the particular compound warrants further evaluation.

Fast-AS倡议的结果有望提高人们对自闭症谱系障碍（ASD）创新药理治疗方法的基本机制的理解和发展。 ASD是一组复杂的神经发育障碍，其严重性范围为，其特征是社会障碍，沟通困难以及受限制，重复和刻板印象的行为模式。该计划旨在迅速测试和分析新的干预措施（即化合物）及其分子和/或临床靶标，用于治疗心理病理学的临床维度（例如，社会参与，刚性或僵化性或僵化性），构成了ASD的核心特征。特别令人感兴趣的是当前DSM-IV-TR诊断实体中所述的ASD的特征，但通常不能被鉴定为当前临床治疗的主要靶标。如上所述，人们对跨传统疾病类别的机制以及相关机制和临床靶标的进行了直接评估，而不是通过分配特定诊断来推断。预计该倡议的结果将通过这种新颖的干预措施增强对特定目标参与的了解，从而开发与ASD相关的精神病理学临床维度的创新治疗方法。在这种情况下，新颖的干预措施（即化合物）可能是指新化学实体（NCE）或正在考虑从其他指示重新使用的化合物。如果最近的基础研究发现表明该化合物有可能影响导致精神疾病的生物学机制，并且以前在临床研究中未经测试的化合物，则对已FDA批准的化合物进行了其他指征（重新修复）的测试（重新进行了）的测试是有趣的。该合同对复制当前销售精神病药物的分子靶标的作用的化合物对本合同不感兴趣。该合同的主要目标是：A。迅速执行小规模和/或IIA期临床试验（例如，首先是人类（FIH）（FIH），临床机制证明（POCM），概念证明（POC），以证明目标参与，安全性和成人良好，或成人的良好范围，以及/或成人，或成人，和/或成人，或/或成人，或/或成人的早期迹象，或与ASD相关的精神病理学临床维度的青少年和/或成年人。 B.取决于可用于测试化合物的试验数据，每个试验可能是一项单点或多站点研究，其中许多受试者足以成功解决主要目标（例如，药物剂量范围，人类的安全性，分子和/或临床目标的安全性，分子和/或临床目标，潜在的生物标志物，潜在的生物标记，生物学效应，有效的迹象，是否有效地签署了一个特定的签名）。