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

Meth-OD：IXT-M200 在甲基苯丙胺过量患者中的 2A 期研究

• 批准号: 10269933
• 负责人: W BROOKS GENTRY
• 金额: $ 375.02万
• 依托单位: INTERVEXION THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269933
• 关键词: Accident and Emergency department; Admission activity; Affect; Affinity; Agitation; Annual Reports; Antibodies; Antibody Therapy; Antidotes; Antipsychotic Agents; Benzodiazepines; Binding; Blood; Brain; Caring; Cessation of life; Clinical Research; Clinical Trials; Cocaine; Data; Delusions; Disease; Documentation; Dose; Enrollment; Feedback; Fentanyl; Freezing; Future; Goals; Hour; Human Volunteers; Intoxication; Lorazepam; Measures; Methamphetamine; Monoclonal Antibodies; Motor Activity; Names; Oral; Outcome; Outcome Study; Overdose; Paranoia; Patients; Pharmaceutical Preparations; Phase; Physicians; Protocols documentation; Randomized; Rattus; Recording of previous events; Reporting; Research; Research Design; Risk; Safety; Sampling; Sedation procedure; Severities; Statistical Data Interpretation; Symptoms; System; Testing; Therapeutic; Time; Vial device; Visit; Work; Writing; animal data; authority; base; clinical practice; cohort; design; effective therapy; efficacy testing; follow-up; indexing; meetings; methamphetamine effect; methamphetamine use; mortality; open label; opioid mortality; overdose death; overtreatment; patient population; psychostimulant; receptor; recruit; reduce symptoms; response; safety and feasibility; sedative; stability testing; symptom treatment; synthetic opioid; treatment as usual; treatment effect

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.

项目摘要 甲基苯丙胺（甲基苯丙胺（Methamine）现在在美国西部的过量死亡人数比任何其他药物都多， 包括芬太尼。虽然阿片类药物过量的死亡人数仍然超过心理刺激剂，但 天然和半合成阿片类药物和可卡因的死亡率正在降低。合成阿片类药物的死亡和 精神刺激剂主要是由于甲基苯丙胺，正在增加。 互动正在开发IXT-M200（一种结合具有高亲和力的甲基的抗体）用于治疗甲基的抗体 使用障碍。它在健康的人类志愿者中似乎是安全的，包括使用甲基苯丙胺的志愿者。 IXT-M200 通过减少甲基分布的量来工作，从而降低脑浓度。非临床 模拟甲基药物过量的研究表明，在大甲剂量后，用抗-METH抗体进行治疗， 迅速降低甲基甲基效果。假设是抗METH抗体治疗将：1）安全使用 甲基甲基甲基酸碱过量的患者导致过量症状及其持续时间的幅度减少， 3）减少减轻过量症状所需的其他药物。 该提案的目的是确定紧急情况下使用IXT-M200的可行性和安全性 部门直接拮抗甲基药物过量。 Meth-OD：IXT-M200的2A期研究 甲基苯丙胺过量患者是一项随机的开放标签研究，旨在比较IXT-M200 像往常一样用劳拉西ep剂量治疗的剂量。到达急诊科的患者 将招募治疗其最近使用甲基苯丙胺的症状。四十名注册受试者将被随机分配 在4个顺序队列中的每一个中，有8个接收单剂量的IXT-M200（200-800 mg，iv）和2个获得1 mg 口服Lorazepam。如果治疗医师认为有必要进行其他药物 在初次治疗后短暂的观察期之后。将收集样品以分析 IXT-M200和甲基血液浓度。将记录搅动分数和生命体征以比较 随着时间的流逝，抗体和劳拉西m的影响。还将比较从治疗到出院的时间。 支持METH-OD研究的活动包括监管提交和制造。所有需要 文档将提交给IXT-M200 IND，包括协议，安全和年度报告以及 临床研究报告。未来研究计划将通过为下一个编写研究协议制定 过量的研究并与FDA会面，讨论并获得反馈。 IXT-M200批次用于 现在可以使用Meth-OD研究，并且在整个项目中将继续进行稳定研究。为 下一个试验，将生产和冷冻500升IXT-M200，以便在需要时可以使用。 这项研究的预期结果包括轻度患者人群的安全性和早期功效数据 甲基药物过量。预测的有效剂量水平应从结果中计算出来，从而实现未来的研究 适当设计以测试急诊科的功效。