New Experimental Medicine Studies: Fast-Fail Trials in Autism Spectrum Disorders

FAST-AS倡议的结果预计将导致对自闭症谱系障碍(ASD)潜在机制的更好理解和创新药物治疗方法的开发。ASD是一组严重程度不等的复杂神经发育障碍，其特征是社交障碍、沟通困难以及受限、重复和刻板印象的行为模式。 这一举措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，以治疗精神病理学的临床层面(例如，社会参与、僵化或僵化)，包括自闭症的核心特征。特别令人感兴趣的是ASD的特征，如当前的DSM-IV-TR诊断实体中所描述的，但通常不被确定为当前临床治疗的主要目标。如上所述，人们有兴趣研究跨越传统障碍类别的机制，其中相关机制和临床目标是直接评估的，而不是通过分配特定诊断来推断的。 这一倡议的结果预计将通过这种新的干预措施加强对特定目标参与的理解，从而为与自闭症相关的精神病理学的临床层面开发创新的治疗方法。在这方面，新的干预措施(即化合物)可以是指新的化学实体(NCEs)，也可以是指正在考虑从其他适应症重新利用的化合物。如果最近的基础研究发现表明化合物(S)有可能影响导致精神障碍的生物机制，并且以前没有在临床研究中进行测试，那么对已被FDA批准用于其他适应症(重新用途)的化合物的测试是有意义的。作用于分子靶点的化合物复制了目前市场上销售的精神药物的分子靶点，对本合同不感兴趣。 本合同的主要目标是： A.迅速进行小规模的I期和/或IIa期临床试验(例如，首个人类临床试验)，以证明这些有希望的干预措施在健康儿童、青少年和/或成人受试者和/或具有ASD相关精神病理学临床维度的儿童、青少年和/或成人队列中的靶向性、安全性和早期有效性迹象。 B.根据可供选择进行测试的化合物的试验数据，每个试验可能是一项单点或多点研究，有许多受试者足以成功地解决主要目标(例如，药物剂量范围、人体安全性、分子和/或临床靶点参与、潜在生物标记物、生物效应、疗效的早期迹象)，并为判断特定化合物是否需要进一步评估提供信息。

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.