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.

InterveXion正在开发一种名为IXT-M200的抗甲基苯丙胺(METH)单抗 冰毒使用障碍的治疗。单剂IXT-M200在健康志愿者中耐受性良好 还有冰毒使用者，他们在服用IXT-M200后每周服用冰毒(30毫克，静脉注射)。 重要的是，我们正在进行的第二阶段研究的中期分析表明，IXT-M200改变了冰毒在 根据非临床数据预测的人类，特别是通过大幅减少冰毒的分配量，即， 将冰毒隔离在血液中。无严重不良事件或超过轻度或中度的不良事件 已在第二阶段研究中报告。 目前提议的长期非临床研究将促进多剂量临床试验以测试IXT-M200 在减少冰毒使用方面的有效性。此外，InterveXion还将改进IXT的制造工艺- M200，从而遵守自IXT-M200开发以来实施的新法规 节目开始了。最后，皮下注射IXT-M200将作为一种潜在的改善进行探索。 给药方案。皮下注射可以在办公室或咨询环境中进行，这样可以 患者更容易接受IXT-M200，并应提高服药依从性。 这项提案的主要目标是将IXT-M200转移到FDA批准过程的下一个里程碑，这 是对人体的多剂量研究，例如关键的2b/3期研究。实现这一目标的具体目标 要达到的目标如下。目标1：制造IXT-M200以支持所需的非临床和临床 学习。单个细胞将被分离并用于生成具有改进生产的新的主细胞库 能力。将生产两批，为AIM 2和即将到来的临床试验提供材料。目标2： 在大鼠身上完成IXT-M200的多剂量研究，以支持人类的多剂量给药。一个 成功后，将对大鼠进行为期6个月的毒理学研究，每周服用27剂IXT-M200 完成了一项试点研究。目的3：进行研究以确定皮下给药的可行性 IXT-M200。IXT-M200将被浓缩到至少140毫克/毫升，并皮下注射给大鼠 注射。将测试抗体的药代动力学、冰毒结合能力和免疫原性。目标4： 通过与FDA沟通，维护IND，并开发，为首次多剂量临床研究做准备 一份完整的临床方案。所有监管互动和要求都将在这一目标下完成，以便 一旦这项工作完成，多剂量临床试验就可能开始。 冰毒使用障碍的治疗仍然是一个未得到满足的医疗需求，目前还没有药物获得美国政府的批准 美国食品和药物管理局。InterveXion继续努力满足这一需求，快速推进 第一个与冰毒结合的单抗IXT-M200。这些研究是满足这一需求的下一步。