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

• 批准号: 9115554
• 负责人: W BROOKS GENTRY
• 金额: $ 208.51万
• 依托单位: INTERVEXION THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115554
• 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; Patient-Focused Outcomes; 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 effect; methamphetamine use; methamphetamine user; novel; patient population; prevent; programs; recidivism; research study; response; safety study; social; stability testing; treatment program

 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（由应用程序提供）：甲基苯丙胺（甲基苯丙胺）滥用在美国和世界上造成严重的医疗，社会和经济伤害。但是，迄今为止，尚未批准药物来治疗甲基成瘾。这个翻译项目的主要目的是对一种新的甲基苯丙基成瘾医学进行安全研究，这是一种称为CH-MAB7F9的新型抗METH单克隆抗体（MAB），以支持甲基苯丙胺使用者的首次临床研究的计划。在非占地健康受试者中对CH-MAB7F9进行1A期研究的结果表明，该抗体对人类的给药是安全的。 CH-MAB7F9的创建是为了选择性地并快速结合血液中的甲基苯酚，并防止其进入大脑，而其他时间会导致多种健康问题，包括成瘾。通过这样做，抗METH CH-MAB7F9将通过提供第一种可以长时间降低甲基甲基苯酚加强特性的药物来改变成瘾的临床治疗。与使用甲基苯丙胺相关的累犯率很高。通过使用长效抗体拮抗剂为甲基甲基苯丙胺的效果提供全天候的保护，患者将不太容易缓解使用甲基甲基苯酚的使用，从而显着提高了恢复的机会。抗药物mAb药物在成瘾疗法方面具有重要的优势，因为即使在免疫受损的患者中，稳态浓度和精确控制剂量也很容易实现，并且因为他们不会与其他药物相互作用。此外，对大多数患者人群的MAB药物是安全的。对于研究和测试计划，CH-MAB7F9将在大鼠的安全性中进行测试，以结合高，暴饮暴食的剂量。此外，将在大鼠中进行甲基苯丙胺自我管理研究，以回答FDA的特定问题，以了解用户克服抗体刺激性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特定目标：1）完成1B期研究的完整基本监管工作； 2）生产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大鼠CH-MAB7F9和METH之间相互作用的安全性，4）在METH自我管理研究中测试CH-MAB7F9，以检查药物使用的动机方面。这些研究对于在甲基苯丙胺使用者中进行1B期研究是必要的，这对于确定确定最佳人类剂量方案的因素至关重要，并且将允许在CH-MAB7F9有效性为主要终点的未来临床研究的有效设计。治疗性的视野是，该药物可用于启动和继续药物治疗，将与高质量的行为修改程序结合使用，以极大地改善患者的结果。