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）的潜在机制和创新药物治疗方法的发展的深入了解。ASD是一组复杂的神经发育障碍，其严重程度不同，其特征在于社交障碍，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）和它们用于治疗精神病理学临床方面的分子和/或临床靶点（例如，社会参与度、刚性或可接受性），其包括ASD的核心特征。特别感兴趣的是ASD的特征，如在当前DSM-IV-TR诊断实体中描述的，但通常不被鉴定为当前临床治疗的主要靶标。如上所述，人们对研究跨越传统疾病类别的机制感兴趣，并且直接评估相关机制和临床靶点，而不是通过指定特定诊断来推断。这一举措的结果预计将导致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ASD相关的精神病理学的临床维度开发创新的治疗方法。在这种情况下，新的干预措施（即，化合物）可以指新的化学实体（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学机制，并且以前未在临床研究中进行过测试，则对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。本合同对作用于分子靶点的化合物不感兴趣，这些分子靶点与目前市售的精神科药物的分子靶点相似。本合同的主要目的是：A。为了迅速开展小规模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）），以证明在健康儿童、青少年和/或成人受试者和/或具有与ASD相关的精神病理学临床维度的儿童、青少年和/或成人的良好表征队列中，此类有希望的干预措施的靶向参与、安全性和早期疗效迹象。B。根据所选化合物的试验数据，每项试验可能是单中心或多中心研究，受试者人数足以成功实现主要目标（例如，药理学剂量范围、在人体中的安全性、分子和/或临床靶标接合、潜在的生物标志物、生物效应、功效的早期迹象），并告知判断特定化合物是否需要进一步评价。

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.