OUTLAST - A First Multiple-Dose Efficacy Study of IXT-m200, an anti-METH Monoclonal Antibody, in Patients with METH Use Disorder

项目摘要 甲基苯丙胺使用障碍(MUD)在美国是一个严重的健康问题，没有批准的药物 接受治疗。本申请旨在检测6-甲基苯丙胺单抗IXT-M200。 对减少甲基苯丙胺复吸的有效性进行一个月的多剂量研究。先前的人体研究 IXT-M200的研究表明，单剂注射是安全的，抗体会改变甲基苯丙胺 通过将其分布体积减少到大约血管空间来实现药代动力学。这是一种隔离 血液中的甲基苯丙胺，并降低其自由进入其他组织的能力，如它所在的大脑 最活跃的。这项提议的主要目标是完成最后的研究，这将是第一次 专门作用于甲基苯丙胺的药物将在有泥浆的人身上进行测试。具体目标是 要满足所有法规要求以维护IXT-M200 IND并准备审批，请完成 持续研究，并通过样品分析和制作支持临床试验。 OutLast研究将在两个连续的队列中招募大约120名患有MUD的参与者。第一 队列将接受1.5克IXT-M200或安慰剂，比例为2：1。在中期分析之后，第二个 队列将接受3g IXT-M200或安慰剂，除非中期分析支持剂量调整。每个人 参与者将接受间隔4周的6剂。在最后一次访问后，后续访问将持续3个月 剂量。每个参与者都将完成认知行为治疗的计算机培训 (CBT4CBT)模块在试用的前两个月。参与者还将有权访问专门的 每周电话/视频通话和工作时间发短信的恢复教练。 在随机和初始剂量后，受试者将通过调查报告他们前一天的药物使用情况 通过智能手机应用程序进行。这款应用程序还将通知受试者，当他们被随机选择进行两次- 每周唾液药物检测。每个受试者都将被运送唾液检测试剂盒，他们将在录音时使用这些试剂盒 当被选中时，他们自己在视频上。将审查视频的有效性，并由Traded记录结果 人事部。 这些药物使用数据，包括自我报告和随机测试，将用于评估主要疗效终点 这是在复发的4周宽限期后20周内戒除兴奋剂的百分比 是被允许的。主要分析将测试每个IXT-M200组和 安慰剂组，使用协方差分析进行估计。 次要终点包括在研究药物治疗的最后一个月期间完全戒烟，从 在第13、25和33周进行的疗效评估中的筛查，以及所测量的安全性 通过体检、生命体征、临床实验室检测和不良事件评估。免疫原性将 也要有决心。

PROJECT ABSTRACT Methamphetamine use disorder (MUD) is a significant health concern in the US with no approved medications for treatment. This application aims to test IXT-m200, an anti-methamphetamine monoclonal antibody, in a 6- month multiple-dose study for efficacy in reducing relapse to methamphetamine use. Previous human studies of IXT-m200 have shown that single doses are safe and the antibody alters methamphetamine pharmacokinetics by reducing its volume of distribution to approximately the vascular space. This sequesters methamphetamine in the blood and reduces its ability to freely enter other tissues such as the brain where it is most active. The main goal of this proposal is to complete the OUTLAST study which will be the first time a medication that specifically acts on methamphetamine will be tested in people with MUD. The specific aims are to fulfill all regulatory requirements to maintain the IXT-m200 IND and prepare for approval, complete the OUTLAST study, and support the clinical trial with sample analysis and manufacturing. The OUTLAST study will enroll approximately 120 participants with MUD in two consecutive cohorts. The first cohort will receive either 1.5 g IXT-m200 or placebo in a 2:1 ratio. Following an interim analysis, the second cohort will receive 3 g IXT-m200 or placebo, unless the interim analysis supports a dose adjustment. Each participant will receive 6 doses spaced 4 weeks apart. Follow-up visits will continue for 3 months after the last dose. Each participant will complete the Computer-Based Training for Cognitive Behavioral Therapy (CBT4CBT) modules during the first two months of the trial. Participants will also have access to a dedicated recovery coach for weekly phone/video calls and texting during business hours. After randomization and initial dosing, subjects will report their previous day’s drug use through a survey conducted via smartphone app. The app will also notify subjects when they are randomly selected for a twice- weekly saliva drug test. Each subject will be shipped saliva testing kits which they will use while recording themselves on video when selected. Videos will be reviewed for validity and the results recorded by trained personnel. These drug use data, both self-report and random testing, will be used to assess the primary efficacy endpoint which is percent of 20 weeks abstinent from stimulants following a 4-week grace period during which relapses are allowed. The primary analysis will be a test of the mean differences between each IXT-m200 group and the placebo group, as estimated using an analysis of covariance. Secondary endpoints include complete abstinence during the last month of study drug treatment, change from screening in the Treatment Efficacy Assessment performed at weeks 13, 25 and 33, and safety as measured by physical exams, vital signs, clinical laboratory testing, and adverse event assessments. Immunogenicity will also be determined.