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 计划的成果预计将加深对自闭症谱系障碍 (ASD) 潜在机制的了解并开发创新的药物治疗方法。自闭症谱系障碍是一组复杂的神经发育障碍，其严重程度各不相同，其特点是社交障碍、沟通困难以及受限、重复和刻板的行为模式。该倡议旨在迅速测试和分析新的干预措施（即化合物）及其分子和/或临床目标，以治疗包含自闭症谱系障碍核心特征的精神病理学临床维度（例如社会参与、僵化或不灵活）。特别令人感兴趣的是当前 DSM-IV-TR 诊断实体中描述的 ASD 特征，但通常不被确定为当前临床治疗的主要目标。如上所述，人们对跨越传统疾病类别的机制的研究很感兴趣，并且直接评估相关机制和临床目标，而不是通过特定诊断的分配来推断。该倡议的成果预计将通过此类新颖的干预措施增强对特定目标参与的理解，从而开发出针对与自闭症谱系障碍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，新的干预措施（即化合物）可能指新的化学实体（NCE）或正在考虑从其他适应症中重新利用的化合物。如果最近的基础研究发现表明化合物有可能影响导致精神障碍的生物机制并且之前未经测试，那么对已获得 FDA 批准用于其他适应症（重新用途）的化合物进行测试是有意义的在临床研究中。作用于复制当前市售精神科药物的分子靶点的化合物不在本合同范围内。该合同的主要目标是： A. 迅速进行小规模 I 期和/或 IIa 期临床试验（例如首次人体试验 (FIH)、临床机制验证 (POCM)、概念验证 (POC)）在健康儿童、青少年和/或成人受试者和/或临床特征良好的儿童、青少年和/或成人队列中证明此类有希望的干预措施的目标参与度、安全性和有效性的早期迹象与 ASD 相关的精神病理学。 B. 根据所选测试化合物的试点数据，每项试验可能是单中心或多中心研究，受试者数量足以成功实现主要目标（例如药理剂量范围、人体安全性、分子和/或临床目标参与、潜在生物标志物、生物效应、早期疗效迹象），并为判断特定化合物是否值得进一步评估提供依据。