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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要目前，在美国西部，甲基苯丙胺 (METH) 导致的服药过量死亡人数比任何其他药物都要多，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，但天然和半合成阿片类药物和可卡因的死亡率正在下降。合成阿片类药物导致的死亡和精神兴奋剂（主要是冰毒）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。它对于健康的人类志愿者（包括使用冰毒的志愿者）似乎是安全的。 IXT-m200 其作用原理是减少冰毒的分布体积，从而降低大脑浓度。非临床模拟冰毒过量的研究表明，在服用大剂量冰毒后，用抗冰毒抗体治疗，快速减少冰毒效应。假设抗 METH 抗体治疗将： 1) 可安全用于服用冰毒过量的患者，2) 减少过量症状的严重程度及其持续时间， 3) 减少缓解用药过量症状所需的额外药物。该提案的目标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、开放标签研究，旨在比较 IXT-m200 照常使用劳拉西泮治疗的剂量。到达急诊科就诊的患者将招募针对他们最近使用冰毒的症状的治疗。四十名入组受试者将被随机分配在 4 个连续队列中的每个队列中，其中 8 人接受单剂量 IXT-m200（200-800 毫克，静脉注射），2 人接受 1 毫克口服劳拉西泮。如果主治医生认为有必要，可以给予额外的药物初始治疗后经过短暂观察期。将收集样本进行分析 IXT-m200 和冰毒血液浓度。将记录躁动评分和生命体征，以比较抗体和劳拉西泮随时间的影响。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。全部需要文件将提交给 IXT-m200 IND，包括方案、安全性和年度报告，以及临床研究报告。未来的研究计划将通过编写下一个研究方案来制定过量研究并与 FDA 会面讨论并获取反馈。 IXT-m200 批次用于 Meth-OD 研究现已开展，稳定性研究将在整个项目中继续进行。为准备下一次试验将生产一批 500L 的 IXT-m200 并冷冻，以便在需要时使用。这项研究的预期结果包括轻度患者群体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根据结果计算出来，以便将来的研究适当设计用于测试急诊室的功效。