Meth-OD: A PHASE 2A STUDY OF IXT-M200 IN METHAMPHETAMINE OVERDOSE PATIENTS

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PROJECT ABSTRACT Methamphetamine (METH) is now involved in more overdose deaths in the US West than any other drug, including fentanyl. While the number of deaths from opioid overdose still exceed that of psychostimulants, the mortality of natural and semi-synthetic opioids and cocaine is decreasing. Deaths from synthetic opioids and psychostimulants, mostly due to METH, are increasing. InterveXion is developing IXT-m200, an antibody that binds METH with high affinity, for the treatment of METH use disorder. It appears to be safe in healthy human volunteers, including those that use METH. IXT-m200 works by reducing the volume of distribution of METH, thereby reducing brain concentrations. Nonclinical studies simulating a METH overdose show that treatment with anti-METH antibodies, after a large METH dose, quickly reduces METH effects. The hypothesis is that anti-METH antibody treatment will: 1) be safe for use in patients with METH overdose, 2) cause a reduction in the magnitude of overdose symptoms and their duration, and 3) decrease the additional medications necessary to alleviate overdose symptoms. The goal of this proposal is to determine the feasibility and safety of using IXT-m200 in the emergency department to directly antagonize METH overdose. Meth-OD: A Phase 2a Study of IXT-m200 in Methamphetamine Overdose Patients is a randomized, open-label study designed to compare IXT-m200 doses to treatment as usual with lorazepam. Patients who arrive at the emergency department seeking treatment for symptoms of their recent METH use will be recruited. Forty enrolled subjects will be randomized in each of 4 sequential cohorts with 8 receiving a single dose of IXT-m200 (200-800 mg, IV) and 2 getting 1 mg oral lorazepam. If deemed necessary by the treating physician, additional medications may be administered following a short observation period subsequent to initial treatment. Samples will be collected to analyze IXT-m200 and METH blood concentrations. Agitation scores and vital signs will be recorded to compare the effects of the antibody and lorazepam over time. The time from treatment to discharge will also be compared. Activities supporting the Meth-OD study include regulatory submissions and manufacturing. All required documentation will be submitted to the IXT-m200 IND including the protocol, safety and annual reports, and the Clinical Study Report. The plan for future studies will be developed by writing the study protocol for the next overdose study and meeting with FDA to discuss and get feedback. The IXT-m200 lot to be used for the Meth-OD study is available now and stability studies will continue throughout this project. To prepare for the next trial, a 500L batch of IXT-m200 will be produced and frozen so that it is ready for use when needed. Expected outcomes from this study include safety and early efficacy data in a population of patients with mild METH overdose. Predicted effective dose levels should be calculable from the results, enabling future studies appropriately designed to test efficacy in the emergency department.