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

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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.