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（METH）现在在美国西部比任何其他药物都涉及更多的过量死亡， 包括芬太尼虽然阿片类药物过量导致的死亡人数仍然超过精神兴奋剂， 天然和半合成类阿片和可卡因的死亡率正在下降。合成阿片类药物和 精神兴奋剂，主要是由于甲基，正在增加。 InterveXion正在开发IXT-m200，一种以高亲和力结合METH的抗体，用于治疗METH 使用障碍。它在健康的人类志愿者中似乎是安全的，包括那些使用METH的人。IXT-m200 通过减少METH的分布体积，从而降低大脑浓度来起作用。非临床 模拟METH过量的研究表明，在大剂量METH后， 快速减少METH效应。假设抗METH抗体治疗将：1）安全用于 METH过量的患者，2）导致过量症状的程度和持续时间减少， 以及3）减少减轻过量症状所需的额外药物。 本提案的目的是确定在紧急情况下使用IXT-m200的可行性和安全性 部门直接对抗甲基过量。Method-OD：IXT-m200在患者中的2a期研究 甲基苯丙胺过量患者是一项随机、开放标签研究，旨在比较IXT-m200 剂量与常规劳拉西泮治疗相同。到急诊室寻求 将招募针对他们最近使用甲氧西林的症状的治疗。将对40例入组受试者进行随机化 在4个连续队列的每一个中，8个接受单剂量IXT-m200（200-800 mg，IV），2个接受1 mg 口服劳拉西泮如果治疗医生认为有必要，可以给予额外的药物 在初始治疗后的短期观察期后。将采集样本进行分析 IXT-m200和METH血液浓度。将记录躁动评分和生命体征， 抗体和劳拉西泮随时间的作用。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申报和生产。所有必需 将向IXT-m200 IND提交文件，包括方案、安全性和年度报告，以及 临床研究报告。未来研究的计划将通过编写下一个研究方案来制定。 过量研究和与FDA会面以讨论和获得反馈。IXT-m200批次将用于 现在可以进行方法-OD研究，稳定性研究将在整个项目中继续进行。做准备 在下一次试验中，将生产500 L批次的IXT-m200并冷冻，以便在需要时使用。 本研究的预期结果包括轻度和中度糖尿病患者人群的安全性和早期疗效数据。 冰毒过量。预测的有效剂量水平应该可以从结果中计算出来，以便将来进行研究。 在急诊科测试其有效性的适当设计。