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: 10425428
• 负责人: W BROOKS GENTRY
• 金额: $ 186.31万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425428
• 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; Documentation; Dose; Enrollment; Feedback; Fentanyl; Freezing; Future; Goals; Hour; Human Volunteers; Intoxication; Lorazepam; Measures; Methamphetamine; Methamphetamine overdose; Methamphetamine use disorder; 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; antagonist; 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 在美国西部，甲基安非他明(冰毒)导致的过量死亡人数比其他任何药物都多， 包括芬太尼。虽然阿片类药物过量造成的死亡人数仍然超过精神刺激剂，但 天然和半合成阿片类药物和可卡因的死亡率正在下降。合成阿片类药物和 精神刺激剂，主要是由于冰毒，正在增加。 InterveXion正在开发IXT-M200，一种以高亲和力结合冰毒的抗体，用于治疗冰毒 使用无序。它似乎在健康的人类志愿者中是安全的，包括那些使用冰毒的志愿者。IXT-M200 工作原理是减少冰毒的分布量，从而降低大脑浓度。非临床 模拟冰毒过量的研究表明，在大剂量冰毒后，用抗冰毒抗体治疗， 迅速减少冰毒的影响。这个假设是，抗冰毒抗体治疗将：1)用于 冰毒过量的患者，2)导致过量症状的程度和持续时间的减少， 以及3)减少缓解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 部门直接对抗冰毒过量。Meth-OD：IXT-M200的2a期研究 甲基苯丙胺过量患者是一项随机开放研究，旨在比较IXT-M200 剂量同往常一样，用劳拉西潘治疗。到急诊科寻求治疗的病人 将招募针对他们最近使用冰毒症状的治疗。40名登记的受试者将被随机分配 在4个序贯队列中，8个接受单剂量IXT-M200(200-800 mg，静脉注射)，2个接受1 mg 口服劳拉西潘。如果主治医师认为有必要，可以加用其他药物。 在最初治疗后的短观察期之后。将采集样本进行分析 IXT-M200和冰毒血液浓度。焦虑评分和生命体征将被记录下来，以比较 随着时间的推移，抗体和劳拉西潘的影响。从治疗到出院的时间也将进行比较。 支持Meth-OD研究的活动包括监管提交和制造。所有必填项 将向IXT-M200 IND提交文件，包括协议、安全和年度报告，以及 临床研究报告。未来研究的计划将通过制定下一次研究的研究方案来制定 过量研究并与FDA会面，讨论并获得反馈。IXT-M200地块将用于 甲基过量研究现已完成，稳定性研究将在整个项目中继续进行。为未来的 下一次试验，将生产一批500升的IXT-M200并进行冷冻，以便在需要时可以使用。 这项研究的预期结果包括轻度糖尿病患者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，从而使未来的研究成为可能 适当设计以测试急诊科的疗效。