Optimization and testing of anti-methamphetamine antibody therapy to support pivotal clinical trials and commercialization

抗甲基苯丙胺抗体疗法的优化和测试以支持关键的临床试验和商业化

• 批准号: 10361540
• 负责人: Misty Ward Stevens
• 金额: $ 211.6万
• 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: 2020-05-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10361540
• 关键词: Active Sites; Advanced Development; Adverse event; Affinity; Annual Reports; Antibodies; Antibody Therapy; Behavioral; Binding; Biological Availability; Bioreactors; Blood; Brain; Cardiovascular system; Cell Line; Cells; Clinic; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Counseling; Data; Development; Dose; Drug Kinetics; Drug abuse; Excipients; Formulation; Goals; Growth; Half-Life; Hepatic; Human; Immune response; Infusion procedures; Kidney; Medical; Medicine; Methamphetamine; Methamphetamine dependence; Methamphetamine use disorder; Monoclonal Antibodies; Outcome; Outpatients; Pathway interactions; Patients; Penetration; Pharmaceutical Preparations; Phase; Pilot Projects; Preparation; Process; Production; Productivity; Professional counselor; Program Development; Protocols documentation; Public Health; Rattus; Regimen; Regulation; Reporting; Route; Running; Safety; Serious Adverse Event; Specific qualifier value; Subcutaneous Injections; Testing; Therapeutic; Therapeutic antibodies; Therapy trial; Time; Toxicology; Update; Work; cell bank; commercialization; design; drug standard; healthy volunteer; immunogenicity; improved; innovation; manufacturing process; medication compliance; meetings; methamphetamine abuse; methamphetamine effect; methamphetamine use; methamphetamine user; miniaturize; phase 1 study; phase 2 study; preclinical study; subcutaneous; treatment program; volunteer

InterveXion is developing an anti-methamphetamine (METH) monoclonal antibody called IXT-m200 for the treatment of METH use disorders. Single doses of IXT-m200 have been well-tolerated in healthy volunteers and also METH users who are given weekly doses of METH (30 mg, IV) following IXT-m200 administration. Importantly, an interim analysis of our ongoing Phase 2 study shows that IXT-m200 alters METH distribution in humans as predicted from nonclinical data, specifically by greatly reducing METH volume of distribution, i.e., sequestering METH in the blood. No serious adverse events or adverse event greater than mild or moderate have been reported in the Phase 2 study. The currently proposed long-term nonclinical studies will facilitate multiple dose clinical trials to test IXT-m200 for efficacy in reducing METH use. In addition, InterveXion will improve the manufacturing process for IXT- m200 and thereby comply with new regulations that have been imposed since the IXT-m200 development program began. Finally, subcutaneous administration of IXT-m200 will be explored as a potential improvement to the dosing regimen. Subcutaneous injections may be given in an office or counseling setting, would allow patients to more easily receive IXT-m200, and should improve medication compliance. The major goal of this proposal is to move IXT-m200 to the next milestone in the FDA approval process, which is multiple dose studies in humans, such as pivotal Phase 2b/3 studies. The specific aims that will allow this goal to be met are as follows. Aim 1: Manufacture IXT-m200 to support required nonclinical and clinical studies. A single cell will be isolated and used to generate a new Master Cell Bank with improved production capabilities. Two batches will be made to provide material for Aim 2 and upcoming clinical trials. Aim 2: Complete multiple dose studies of IXT-m200 in rats to support multiple dose administration in humans. A 6-month toxicology study with 27 weekly doses of IXT-m200 in rats will be done following the successful completion of a pilot study. Aim 3: Conduct studies to determine the feasibility of subcutaneous administration of IXT-m200. IXT-m200 will be concentrated to at least 140 mg/mL and given to rats by subcutaneous injection. Antibody pharmacokinetics, METH binding capability and immunogenicity will be tested. Aim 4: Prepare for first multiple dose clinical study by communicating with FDA, maintaining the IND, and developing a full clinical protocol. All regulatory interactions and requirements will be completed under this aim so that a multiple dose clinical trial may begin as soon as this work is completed. The treatment of METH use disorder remains an unmet medical need with no medications yet approved by the US FDA. InterveXion continues to strive to meet this need by pushing forward quickly with the development of the first METH-binding mAb, IXT-m200. These studies are the next steps toward meeting that need.

互动正在开发一种抗甲基苯丙胺（METH）单克隆抗体，称为Ixt-M200 甲基甲基苯丙胺的治疗障碍。单剂量的IXT-M200在健康的志愿者中得到了良好的耐受性 以及在IXT-M200管理后每周给予甲基甲基苯丙胺（30 mg，iv）的甲基苯丙胺使用者。 重要的是，对我们正在进行的2阶段研究的临时分析表明，IXT-M200改变了METH的分布 人类正如非临床数据所预测的那样，特别是通过大大减少了分布的量，即 隔离血液中的甲基苯丙胺。没有严重的不良事件或不良事件大于轻度或中度 在第二阶段研究中已有报道。 目前提出的长期非临床研究将促进多次剂量临床试验测试IXT-M200 用于减少甲基苯丙胺的功效。此外，互动将改善IXT-的制造过程 M200，因此符合自IXT-M200开发以来施加的新法规 计划开始。最后，将探索IXT-M200的皮下给药，以作为潜在的改进 给剂量方案。皮下注射可以在办公室或咨询环境中进行，将允许 患者更容易获得IXT-M200，并应提高药物依从性。 该提案的主要目标是将IXT-M200移至FDA批准过程中的下一个里程碑， 是人类的多次剂量研究，例如关键阶段2B/3研究。将允许这一点的具体目标 要满足的目标如下。目标1：制造IXT-M200以支持需要非临床和临床 研究。一个单元将被隔离，并用于生成具有改善生产的新的主电池库 功能。将批量两批为AIM 2和即将进行的临床试验提供材料。目标2： 完成大鼠IXT-M200的多次剂量研究，以支持人类多剂量给药。一个 成功的6个月毒理学研究将在成功之后完成大鼠的27剂IXT-M200剂量 试点研究的完成。目标3：进行研究以确定皮下给药的可行性 IXT-M200。 IXT-M200将集中至至少140 mg/ml，并通过皮下给予大鼠 注射。将测试抗体药代动力学，METH结合能力和免疫原性。目标4： 通过与FDA沟通，维护IND并发展为第一次多剂量临床研究做准备 完整的临床方案。所有监管互动和要求都将在此目标下完成，以便 这项工作完成后，多剂量临床试验可能会开始。 甲基甲基甲基苯丙胺的治疗仍然是未满足的医疗需求，没有药物 美国FDA。互动继续努力通过随着发展的发展而迅速前进 第一个冰毒结合mab，ixt-m200。这些研究是满足需求的下一步。