Phase 1a/1b Clinical Trials of Multivalent Opioid Vaccine Components

项目摘要 目前，滥用处方阿片类镇痛药和海洛因在美国是一个普遍的问题。 几种药物，包括美沙酮，丁丙诺啡和纳洛酮，是可用的，有效的， 治疗阿片类药物使用障碍（OUD），长期复发率仍然很高。目前的研究旨在 检查治疗OUD的新方法，即使用靶向羟考酮的疫苗（OXY-KLH）， 最常滥用的处方阿片类药物之一，以及针对 海洛因/吗啡。最终，将开发一种双价疫苗（OXY-KLH和M-KLH）， 羟考酮和海洛因这项研究的长期目标是开发一种多价疫苗， 羟考酮海洛因和其他相关阿片类药物然而，在我们的IND前会议上，FDA/CBER要求 在开发二价疫苗之前，我们要分别研究每种疫苗。的 本申请提出了一项1a/1b期研究，旨在评价安全性（目的1）、免疫原性 (Aim 2），和初步疗效（目标3）的OXY-KLH在UG 3阶段的授权期（研究1）， 在授权期的UH 3阶段进行的M-KLH的类似1a/1b期研究（研究2）。过渡到 将在安全性、免疫原性和初步疗效分析后确定UH 3阶段 对OXY-KLH疫苗进行了研究。总体而言，拟议的研究将提供大量信息 关于疫苗在减少阿片类药物滥用方面的安全性和潜在功效， 在受控的实验室环境中进行。如果拟议的OXY-KLH和M- KLH是有利的，我们将继续开发二价疫苗（OXY-KLH加M-KLH）。

Project Summary Currently, abuse of prescription opioid analgesics and heroin is a pervasive problem in the U.S. Although several medications, including methadone, buprenorphine, and naltrexone, are available and effective in treating opioid use disorder (OUD), long-term relapse rates remain high. The current studies are designed to examine a novel approach to treating OUD, namely use of a vaccine (OXY-KLH) targeted against oxycodone, one of the most commonly abused prescription opioids, and a vaccine (M-KLH) targeted against heroin/morphine. Ultimately, a bivalent vaccine (OXY-KLH and M-KLH) will be developed that will target oxycodone and heroin. The long-term goal of this research is to develop a multivalent vaccine directed against oxycodone, heroin, and other relevant opioids. However, during our pre-IND meeting, the FDA/CBER asked that we study each vaccine separately before moving forward with development of the bivalent vaccine. The current application proposes a Phase 1a/1b study designed to evaluate the safety (Aim 1), immunogenicity (Aim 2), and preliminary efficacy (Aim 3) of OXY-KLH during the UG3 phase of the grant period (Study 1) and a similar Phase 1a/1b study of M-KLH during the UH3 phase of the grant period (Study 2). Transition to the UH3 phase will be determined after safety, immunogenicity, and preliminary efficacy analyses have been performed for the OXY-KLH vaccine. Overall, the proposed studies will provide a great deal of information about the safety and potential efficacy of the vaccines in reducing the abuse liability of opioids, which will be administered in a controlled laboratory setting. If the outcomes of the proposed studies with OXY-KLH and M- KLH are favorable, we will proceed with development of the bivalent vaccine (OXY-KLH plus M-KLH).