The US FDA has not approved any medications for the treatment of methamphetamine (METH) use disorders. Currently, cognitive-behavioral and contingency-management interventions are the most effective treatments. IXT-m200, a monoclonal antibody that specifically binds METH in the blood, is being developed as a pharmacological treatment for use in conjunction with behavior therapies. Based on nonclinical studies, IXT-m200 is expected to alter METH pharmacokinetics in human subjects resulting in reduced or blocked METH subjective effects that reinforce METH use. STAMPOUT, a Phase 2a Study of Antibody for Methamphetamine Outpatient Therapy, will provide proof-of-concept that IXT-m200 can alter METH disposition. This is needed before a large efficacy study can be done. This application proposes the first clinical study in METH users of a biological medication developed specifically for patients with METH use disorders. The primary goal of this application is to show that a METH antibody will alter the pharmacokinetics of METH in users and reduce the reinforcing subjective effects that perpetuate METH use. During the STAMPOUT study, METH-using subjects will receive single doses of IXT-m200 followed by weekly METH challenges. Serial blood samples and urine collections will be analyzed to determine the METH pharmacokinetic changes due to the antibody dose. Drug effects questionnaires given after METH challenges will quantify the impact of IXT-m200 on the subjective effects of METH. These data will be used to determine the minimum serum concentration of IXT-m200 necessary for reducing reinforcing subjective effects of METH. Also during this project, there will be interaction with the FDA and the overall clinical development plan will be advanced by planning for a Phase 2b/3 clinical study in larger groups of users who wish to quit using METH. Stability testing of the IXT-m200 drug product will continue throughout the study, along with additional manufacturing work as necessary to support the STAMPOUT study. A highly experienced, transdisciplinary academic and industry team will accomplish the following Specific Aims: 1) Advance the clinical development of IXT-m200 by interacting with FDA and planning for future studies, 2) Complete STAMPOUT, a Phase 2a Study of Antibody for Methamphetamine Outpatient Therapy, and 3) Perform manufacturing tasks required to support a clinical study of IXT-m200. STAMPOUT is a turning point. With proof-of-concept data, plans can be made to study long-term efficacy of IXT-m200 in helping METH users quit and move this game changing medication toward the market and the patients who need it.
The STAMPOUT study in this proposal will be the first study of an anti-METH mAb in METH users, and is a proof-of-concept study that could provide evidence that other immunotherapies can work, potentially changing clinical practice entirely. We will have the opportunity to determine whether the reinforcing effects of METH can be blocked by a mAb through pharmacokinetic antagonism and the minimum concentrations required for this function. Understanding how this mAb works and how effective it is will help determine how other antagonists could be used as adjunctive treatments for substance use disorders.