A Methamphetamine Conjugate Vaccine: From Manufacturing to IND

甲基苯丙胺结合疫苗：从制造到 IND

基本信息

批准号：
8916074
负责人：
Samuel Michael Owens
金额：
$ 184.34万
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：
2014-09-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8916074
关键词：
Active Immunization Adjuvant Adjuvant Study Adverse effects Affinity Animal Model Animal Testing Antibodies Arkansas Behavior Therapy Behavioral Brain Carrier Proteins Characteristics Chemical Structure Chemistry Clinical Clinical Protocols Clinical Research Clinical Trials Clinical trial protocol document Cocaine Cocaine Dependence Conjugate Vaccines Consent Forms Coupled Data Development Dose Drug usage Evaluation Research Funding Goals Haptens Health Human Immune system Immunization Immunotherapy Institutes Institution Investigational New Drug Application Knowledge Lead Legal patent Medical Methamphetamine Methamphetamine dependence Monoclonal Antibodies National Institute of Drug Abuse Nicotine Nicotine Dependence Outcome Pamphlets Patients Performance Pharmaceutical Preparations Pharmacology and Toxicology Phase Phase I Clinical Trials Preclinical Testing Preparation Process Production Protocols documentation Publishing Qualifying Rattus Rehabilitation therapy Relapse Reporting Research Research Contracts Research Personnel Review Committee Rewards Rodent Safety Science Site System Testing Therapeutic Therapeutic Equivalency Time Tissues Toxic effect Toxicology Universities Vaccine Clinical Trial Vaccine Design Vaccines Vendor Work Writing addiction analytical method base clinical lot clinical research site cost design experience gene therapy human study human subject improved innovation large scale production manufacturing process meetings methamphetamine abuse methamphetamine use multidisciplinary next generation novel vaccines polyclonal antibody pre-clinical preclinical study prevent recidivism safety testing scale up social stability testing success treatment program vaccine development vaccine evaluation

项目摘要

DESCRIPTION (provided by applicant): Abuse of methamphetamine (METH) exacts significant medical and social costs in the US and worldwide; yet, there are no medications approved for the treatment of METH addiction. Immunization of addicted patients with a METH-conjugate vaccine (MCV) is a promising new strategy that could stimulate a patient's own immune system to generate long acting, protective anti-METH antibodies. These antibodies would block or slow the rate at which METH enters the brain, shield the user from METH's rewarding and toxic effects, and thereby reduce the medical consequences of relapse to METH use during rehabilitation therapy. The purpose of the proposed work is to scale-up the manufacturing process to produce an MCV, test the MCV in toxicology studies to show its safety, and complete plans for a first in human clinical trial. The candidate MCV was developed and optimized at the University of Arkansas for Medical Sciences (UAMS) where extensive preclinical animal testing demonstrated both safety and efficacy. Vaccines for treating nicotine and cocaine addiction have already been tested in humans, with positive outcomes for those patients making large quantities of anti-drug antibodies. This innovative new MCV, in combination with a state of the art adjuvant, is expected to stimulate significantly higher antibody titers with very high affinity for METH. The important characteristics of this MCV include a rigorously tested and optimized METH hapten chemical structure, refined chemistry for the conjugation of METH hapten to an immunostimulatory carrier protein, and a next generation adjuvant that rapidly generates high titers of anti- METH antibodies. Together, the hapten, carrier protein and adjuvant are essential parameters that determine the success of a vaccine; this MCV fulfills them all. The ultimate goal of this project is to submit a successful investigational new drug application (IND) to the FDA. To reach this goal, the team from InterveXion Therapeutics and UAMS, along with several highly qualified vendors, will accomplish four specific aims. First, the manufacturing platform will be scaled-up and data will be generated to show that the production system is reliable and the MCV is stable during storage. Once proven, a batch of MCV suitable for use in humans will be produced. Second, toxicology studies in rats will provide support for the expected safe administration of MCV with adjuvant to humans. Third, a protocol and all supporting documents for the first clinical trial wil be developed to show the safety and tolerability of the MCV in human subjects. Finally, the IND package will be written, assembled, and submitted to the FDA. At the conclusion of the proposed work, this team will be poised to initiate the first clinical trial for an active METH vaccine.

描述（由申请人提供）：滥用甲基苯丙胺 (METH) 在美国和全世界造成巨大的医疗和社会成本；然而，还没有批准用于治疗冰毒成瘾的药物。使用冰毒结合疫苗（MCV）对成瘾患者进行免疫是一种有前景的新策略，可以刺激患者自身的免疫系统产生长效、保护性抗冰毒抗体。这些抗体会阻止或减慢冰毒进入大脑的速度，保护使用者免受冰毒的有益和毒性作用，从而减少康复治疗期间冰毒复发的医疗后果。拟议工作的目的是扩大 MCV 的生产工艺，在毒理学研究中测试 MCV 以证明其安全性，并完成首次人体临床试验的计划。候选 MCV 是在阿肯色医学大学 (UAMS) 开发和优化的，广泛的临床前动物测试证明了安全性和有效性。用于治疗尼古丁和可卡因成瘾的疫苗已经在人体中进行了测试，对产生大量抗药物抗体的患者产生了积极的结果。这种创新的新型 MCV 与最先进的佐剂相结合，预计会刺激显着更高的抗体滴度，并且对 METH 具有非常高的亲和力。该 MCV 的重要特征包括经过严格测试和优化的 METH 半抗原化学结构、用于将 METH 半抗原与免疫刺激载体蛋白缀合的精细化学，以及可快速产生高滴度抗 METH 抗体的下一代佐剂。半抗原、载体蛋白和佐剂共同构成了决定疫苗成功与否的重要参数。这款 MCV 满足了所有这些要求。该项目的最终目标是向 FDA 提交成功的新药研究申请 (IND)。为了实现这一目标，InterveXion Therapeutics 和 UAMS 的团队以及几家高素质供应商将实现四个具体目标。首先，将扩大制造平台并生成数据，以表明生产系统可靠且MCV在存储期间稳定。一旦得到证实，将生产一批适合人类使用的 MCV。其次，大鼠毒理学研究将为人类预期安全施用 MCV 佐剂提供支持。第三，将制定首次临床试验的方案和所有支持文件，以证明 MCV 在人类受试者中的安全性和耐受性。最后，IND 包将被编写、组装并提交给 FDA。在拟议工作结束后，该团队将准备启动活性冰毒疫苗的首次临床试验。