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

OUTLAST - IXT-m200（一种抗冰毒单克隆抗体）在冰毒使用障碍患者中的​​首次多剂量疗效研究

• 批准号: 10686245
• 负责人: W BROOKS GENTRY
• 金额: $ 460.99万
• 依托单位: INTERVEXION THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686245
• 关键词: Abstinence; Adverse event; Affinity; Analysis of Covariance; Antibodies; Area; Behavior Therapy; Binding; Blood; Blood Vessels; Brain; Bupropion; Businesses; Circulation; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Cognitive Therapy; Communication; Communities; Computers; Country; Data; Data Analyses; Dedications; Diagnostic Reagent Kits; Dose; Dose Limiting; Drug Kinetics; Drug usage; E-learning; Enrollment; FDA approved; Family; Funding; Goals; Grant; Health; Hour; Human; Human Resources; Immunotherapy; Individual; Laboratories; Marketing; Measures; Methamphetamine; Methamphetamine use disorder; Methods; Midwestern United States; Mirtazapine; Monoclonal Antibodies; Naltrexone; Notification; Outcome; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase III Clinical Trials; Placebo Control; Placebos; Preparation; Program Development; Protocols documentation; Quality of life; Random Allocation; Randomized; Rattus; Recovery; Regulation; Relapse; Reporting; Research; Safety; Saliva; Sampling; Statistical Data Interpretation; Stimulant; Surveys; Telephone; Testing; Text; Text Messaging; Time; Tissues; Toxic effect; Training; Treatment Efficacy; United States; Update; Vial device; Visit; clinical material; cohort; design; drug testing; effective therapy; efficacy evaluation; efficacy study; expectation; follow-up; healthy volunteer; immunogenicity; improved; manufacture; meetings; methamphetamine use; methamphetamine user; negative affect; phase 3 study; placebo group; randomized placebo controlled study; salivary assay; screening; secondary endpoint; small molecule; smartphone application; stability testing; video chat

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.

项目摘要 甲基苯丙胺使用障碍 (MUD) 在美国是一个重大的健康问题，目前尚无批准的药物 该应用旨在测试 IXT-m200（一种抗甲基苯丙胺单克隆抗体）的 6- 为期一个月的多剂量研究，旨在降低先前的人体研究中甲基苯丙胺使用的复发。 IXT-m200 的研究表明单剂量是安全的，并且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调节药代动力学。 血液中的甲基苯丙胺会降低其自由进入其他组织（例如其所在的大脑）的能力 该提案的主要目标是完成 OUTLAST 研究，这将是首次 专门针对甲基苯丙胺的药物将在 MUD 患者中进行测试，其具体目标是。 为了满足维护 IXT-m200 IND 并准备批准的所有监管要求，请完成 OUTLAST 研究，并通过样品分析和制造支持临床试验。 OUTLAST 研究将在两个连续队列中招募大约 120 名 MUD 参与者。 中期分析后，第二组患者将按 2:1 的比例接受 1.5 g IXT-m200 或安慰剂。 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。 参与者将接受 6 剂疫苗，间隔 4 周，最后一次随访将持续 3 个月。 每个参与者将完成基于计算机的认知行为治疗培训。 (CBT4CBT) 模块在试用的前两个月内，参与者还可以使用专用的模块。 每周在工作时间内进行电话/视频通话和短信的恢复教练。 随机分组和初始给药后，受试者将通过调查报告前一天的药物使用情况 通过智能手机应用程序进行，当受试者被随机选择进行两次时，该应用程序也会通知受试者。 每周进行唾液药物测试。每个受试者都会收到唾液测试套件，他们将在记录时使用。 选定后，将在视频中审核视频的有效性并由经过培训的人员记录结果。 人员。 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（在此期间复发）之后 20 周戒除兴奋剂的百分比 主要分析将测试每个 IXT-m200 组与对照组之间的平均差异。 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断、从 第 13、25 和 33 周进行的治疗效果评估中的筛查以及测量的安全性 通过体检、生命体征、临床实验室测试和免疫原性评估。 也可以确定。