A Methamphetamine Conjugate Vaccine: From Manufacturing to IND

甲基苯丙胺结合疫苗：从制造到 IND

• 批准号: 8516704
• 负责人: Samuel Michael Owens
• 金额: $ 360.68万
• 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: 2014-09-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516704
• 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; multidisciplinary; next generation; novel vaccines; polyclonal antibody; pre-clinical; preclinical study; prevent; public health relevance; recidivism; safety testing; scale up; social; stability testing; success; treatment program; vaccine development; vaccine evaluation

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）：甲基苯丙胺（METH）的滥用在美国和世界范围内需要大量的医疗和社会成本;然而，没有药物被批准用于治疗METH成瘾。用METH缀合物疫苗（MCV）对成瘾患者进行免疫接种是一种有前途的新策略，其可以刺激患者自身的免疫系统产生长效的保护性抗METH抗体。这些抗体将阻断或减缓METH进入大脑的速率，保护使用者免受METH的奖励和毒性作用，从而减少康复治疗期间METH使用复发的医疗后果。拟议工作的目的是扩大生产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是在阿肯色州大学医学科学（UAMS）开发和优化的，其中广泛的临床前动物试验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，对那些产生大量抗药抗体的患者产生了积极的结果。这种创新的新MCV与最先进的佐剂组合，预期将刺激显著更高的抗体滴度，对METH具有非常高的亲和力。该MCV的重要特征包括严格测试和优化的METH半抗原化学结构、用于将METH半抗原缀合至免疫刺激性载体蛋白的精细化学、以及快速产生高滴度抗METH抗体的下一代佐剂。总之，半抗原、载体蛋白和佐剂是决定疫苗成功的基本参数;这种MCV满足所有这些要求。 该项目的最终目标是向FDA提交成功的研究性新药申请（IND）。为了实现这一目标，InterveXion Therapeutics和UAMS的团队，沿着几个高素质的供应商，将实现四个具体目标。首先，制造平台将按比例扩大，并将生成数据以显示生产系统是可靠的，MCV在存储期间是稳定的。一旦得到证实，将生产一批适用于人类的MCV。第二，大鼠毒理学研究将为MCV与佐剂对人类的预期安全给药提供支持。第三，将开发用于第一临床试验的方案和所有支持性文件，以显示MCV在人类受试者中的安全性和耐受性。最后，IND包装将被编写、组装并提交给FDA。在拟议的工作结束时，该小组将准备启动第一个活性METH疫苗的临床试验。