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）在美国是一个重要的健康问题，没有批准的药物 接受治疗本申请旨在测试IXT-m200，一种抗甲基苯丙胺单克隆抗体，在6- 一项为期一个月的多次给药研究，以评估减少甲基苯丙胺使用复发的疗效。先前的人类研究 IXT-m200的研究表明，单剂量是安全的，抗体改变了甲基苯丙胺 通过将其分布容积减少到大约血管空间来改善药代动力学。这种隔离 血液中的甲基苯丙胺，并降低其自由进入其他组织，如大脑的能力，它是 最活跃的该提案的主要目标是完成OUTLAST研究，这将是第一次 专门作用于甲基苯丙胺的药物将在MUD患者中进行测试。具体目标是 为了满足所有监管要求，以维护IXT-m200 IND并准备批准，请填写 OUTLAST研究，并支持样品分析和制造的临床试验。 OUTLAST研究将在两个连续队列中入组约120例MUD受试者。第一 队列将以2：1的比例接受1.5 g IXT-m200或安慰剂。在中期分析之后，第二次 队列将接受3 g IXT-m200或安慰剂，除非中期分析支持剂量调整。每个 受试者将间隔4周接受6剂。随访访视将在最后一次访视后持续3个月 次给药结束每位参与者将完成认知行为治疗的计算机培训 （CBT 4CBT）模块在试验的前两个月。与会者还将获得一个专门的 恢复教练每周电话/视频通话和短信在工作时间。 在随机化和首次给药后，受试者将通过调查报告其前一天的药物使用情况 通过智能手机应用程序进行。该应用程序还将在受试者被随机选择两次时通知受试者- 每周一次的唾液药检每个受试者将被运送唾液检测试剂盒，他们将使用，而记录 在视频中被选中。将审查视频的有效性，并由经过培训的人员记录结果。 人员的 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4周的宽限期后20周内戒断兴奋剂的百分比， 是允许的。主要分析将是检验每个IXT-m200组与 安慰剂组，使用协方差分析估计。 次要终点包括研究药物治疗最后一个月期间的完全戒断， 在第13、25和33周进行的治疗疗效评估中的筛选，以及测量的安全性 通过体格检查、生命体征、临床实验室检查和不良事件评估。免疫原性将 也要坚决。

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.