Transition to Human Phase 1b Trials: Nonclinical Studies of an Anti-METH mAb

过渡到人体 1b 期试验：抗 METH 单克隆抗体的非临床研究

基本信息

批准号：
8926379
负责人：
W BROOKS GENTRY
金额：
$ 159.49万
依托单位：
INTERVEXION THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8926379
关键词：
Affinity Antibodies Behavior Behavior Therapy Behavioral Binding Blood Brain Cardiovascular system Chronic Clinical Research Clinical Treatment Cocaine Collaborations Data Development Dose Drug Kinetics Drug abuse Drug usage Economics Engineering Extinction (Psychology)Future Goals Grant Half-Life Health Human Immune Immunoglobulin G Industry Medical Medicine Methamphetamine Methamphetamine dependence Modeling Monoclonal Antibodies Motivation Mus Outcome Patients Pharmaceutical Preparations Phase Preparation Process Property Protocols documentation Public Health Rattus Recovery Regimen Relapse Reporting Research Research Design Safety Self Administration Self-Administered Serious Adverse Event Site Teleconferences Testing Therapeutic Time Tissues Toxic effect Toxicology United States Food and Drug Administration Update Vaccines Vision Work addiction cardiovascular risk factor design experience hemodynamics human study improved innovation meetings methamphetamine abuse methamphetamine use novel patient population prevent programs recidivism research study response safety study social stability testing treatment program

项目摘要

DESCRIPTION (provided by applicant): Methamphetamine (METH) abuse causes serious medical, social, and economic harm in the USA and the world. However, to date, no medications are approved to treat METH addiction. The primary goal of this translational project is to conduct safety studies of a new medicine for METH addiction, a novel anti- METH monoclonal antibody (mAb) called ch-mAb7F9, to support the initiation of a first clinical study in METH users. Results from a Phase 1a study of ch-mAb7F9 in non-METH-using healthy subjects indicate that the antibody is safe for administration in humans. Ch-mAb7F9 was created to selectively and quickly bind METH in the blood and prevent it from entering the brain and other tissues where it causes multiple health problems, including addiction. By so doing, anti-METH ch-mAb7F9 will transform the clinical treatment of addiction by providing the first medication that can reduce METH's reinforcing properties for prolonged periods of time. There is a high rate of recidivism associated with METH use. By using a long-acting antibody antagonist to provide around-the-clock protection from METH effects, patients will be much less vulnerable to relapse to METH use and thereby have significantly improved chances for recovery. Anti-drug mAb medications have major advantages for addiction therapy since steady-state concentrations and precise control of dosing are readily achievable even in immune compromised patients, and because they will not interact with other medicines. Furthermore, mAb medications are safe for most patient populations. For the research and testing program, ch-mAb7F9 will be tested in rats for safety in combination with high, binge-like doses of METH. Additionally, METH self-administration studies in rats will be performed to answer specific questions from the FDA concerning the motivation and ability of users to overcome the antibody's stimulant blocking effects. A highly experienced, trans disciplinary academic and industry team will accomplish the following Specific Aims: 1) complete essential regulatory work in preparation for a Phase 1b study; 2) manufacture ch-mAb7F9 for necessary nonclinical and future clinical studies, 3) conduct nonclinical testing to determine safety of the interaction between ch-mAb7F9 and METH in rats, and 4) test ch-mAb7F9 in METH self-administration studies to examine the motivational aspect of drug use. These studies are necessary to prepare for a Phase 1b study in METH users that will be crucial for identifying factors that determine optimal human dosing regimens and will allow for the effective design of future clinical studies where ch-mAb7F9 efficacy is the primary endpoint. The therapeutic vision is that this medication, which can be used to initiate and continue pharmacologic treatment, will be used in combination with high quality behavioral modification programs to dramatically improve patient outcomes.

描述（由申请人提供）：甲基苯丙胺 (METH) 滥用在美国和世界范围内造成严重的医疗、社会和经济危害。然而，迄今为止，还没有药物被批准用于治疗甲基苯丙胺成瘾。该转化项目的主要目标是。对一种治疗冰毒成瘾的新药（一种名为 ch-mAb7F9 的新型抗冰毒单克隆抗体 (mAb)）进行安全性研究，以支持在冰毒使用者中启动第一项临床研究。 1 对不使用冰毒的健康受试者进行的 ch-mAb7F9 研究表明，该抗体可安全用于人体，其目的是选择性地快速结合血液中的冰毒，并防止其进入大脑和其他组织。它会导致多种健康问题，包括成瘾。通过这样做，抗 METH ch-mAb7F9 将提供第一种可以长时间降低 METH 增强特性的药物，从而改变成瘾的临床治疗。与冰毒使用相关的高复发率通过使用长效拮抗剂抗体提供全天候保护，免受冰毒影响，患者将更不易因冰毒使用而复发，从而显着提高康复机会。抗药单克隆抗体药物对于成瘾治疗具有重大优势，因为即使在免疫受损的患者中也可以轻松实现稳态浓度和精确的剂量控制，并且因为它们不会与其他药物相互作用，此外，单克隆抗体药物对于大多数患者群体是安全的。。在研究和测试项目中，将在大鼠中测试 ch-mAb7F9 与高剂量 METH 联合使用的安全性。此外，还将在大鼠中进行 METH 自我给药研究，以回答 FDA 提出的有关 METH 的具体问题。用户克服抗体的兴奋剂阻断效应的动机和能力经验丰富的跨学科学术和行业团队将实现以下具体目标：1) 完成 1b 期研究的必要监管工作； ch-mAb7F9 用于必要的非临床和未来临床研究，3) 进行非临床测试以确定 ch-mAb7F9 与 METH 在大鼠中相互作用的安全性，以及 4) 在 METH 自我给药研究中测试 ch-mAb7F9，以检查其动机方面这些研究对于准备 METH 使用者的 1b 期研究是必要的，这对于确定确定最佳人体给药方案的因素至关重要，并将允许有效的设计。未来以 ch-mAb7F9 疗效为主要终点的临床研究的治疗愿景是，这种可用于启动和继续药物治疗的药物将与高质量的行为矫正计划结合使用，以显着改善患者的治疗结果。