CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS

CD4 IGG2 和 HUMAB 组合的临床试验

• 批准号: 2887738
• 负责人: PAUL J MADDON
• 金额: $ 54.6万
• 依托单位: PROGENICS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887738
• 关键词: AIDS therapy; HIV envelope protein gp120; antigen antibody reaction; clinical research; clinical trial phase I; combination therapy; drug screening /evaluation; human immunodeficiency virus 1; human subject; human therapy evaluation; immunoglobulin G; immunological substance; monoclonal antibody; neutralizing antibody; passive immunization; virus receptors

DESCRIPTION: (Adapted from the applicant's abstract) The development of safe and effective passive immunotherapies for the treatment and prevention of HIV-1 infection is a major goal. The leading candidate immunotherapeutics include the broadly neutralizing human monoclonal antibodies (HuMAbs) IgG1b12, to the CD4-binding site on gp120, 2F5 to a conserved epitope on gp41, and 2g12 to a discontinuous region on gp120. In addition, CD4-IgG2 exhibits potent and broad neutralization of HIV-1, including primary isolates. It is a third generation CD4- based molecule containing two chains of a CD4-human IgG2 heavy chain fusion protein and two chains of a CD4-human kappa light chain fusion protein. While IgG1b12, 2F5, 2G12 and CD4-IgG2 exhibit significant neutralization activity as single agents, the development of an effective passive immunotherapy may require the use of mixtures of two or more of these agents. In order to evaluate their performance in the clinical setting, we have formed a consortium of the three groups which developed these agents (IgG1b12 - Dr. Dennis Burton; 2F5 and 2G12 - Dr. Hermann Katinger; and, CD4-IgG2 - Drs. Graham Allaway and Paul Maddon) to coordinate and expedite clinical trials of single agents and combinations of agents. The goal of this proposal is to manufacture, prepare Investigational New Drug applications and gain regulatory approval for clinical investigation from the U.S. Food and Drug Administration, and perform clinical trials of the agents to evaluate tolerability, antiviral activity, and pharmacology in HIV-1 infected adults and children. As part of our clinical development program, we have already arranged for certain pilot Phase I clinical trials to be performed with single agents in 1997-98 under the sponsorship of the National Institute of Allergy and Infectious Diseases. Based on their performance in clinical trials as well as in in vitro, ex vivo, and animal studies performed as separate projects at the Aaron Diamond AIDS Research Center and the Scripps Research Institute, we will select an optimum combination of 2, 3, or 4 of the agents for evaluation in Phase I/II clinical trials in HIV-1 infected adults and children. If successful, then subsequent to this proposal, the optimum combination would be taken to large-scale, pivotal clinical trials in order to gain marketing approval for the product.

描述：(改编自申请人的摘要)开发 安全有效的被动免疫疗法用于治疗和 预防艾滋病毒-1感染是一个主要目标。领先的候选人 免疫疗法包括广泛中和的人类单抗 针对gp120、2F5和gp120上的CD4结合部位的抗体(HuMAbs)IgG1b12 Gp41上的保守表位，以及2g12上的不连续区域 Gp120。此外，CD4-IgG2显示出强大而广泛的中和作用。 包括初级分离株在内的HIV-1病毒。这是第三代CD-4 含有两条CD4-人IgG2重链的分子 融合蛋白与CD4-人kappa轻链融合的双链 蛋白。 而IgG1b12、2F5、2G12和CD4-IgG2表现出显著的中和作用 作为单剂主动，发展有效的被动 免疫疗法可能需要使用两种或两种以上的混合物。 探员们。为了评估他们在临床环境中的表现， 我们已经组成了一个由三个小组组成的财团，开发了这些 代理(IgG1b12-Dennis Burton博士；2F5和2G12-Hermann博士 以及，CD4-IgG2-Graham Allaway和Paul Maddon博士)到 协调和加快单药和单药的临床试验 代理的组合。这项提议的目标是制造， 准备研究性新药申请并获得监管 美国食品和药物管理局批准进行临床研究 给药，并进行药物的临床试验以评估 HIV-1感染患者的耐受性、抗病毒活性和药理学 成人和儿童。作为我们临床开发计划的一部分，我们 已经安排了某些试点I期临床试验 在1997-98年度由 国家过敏症和传染病研究所。基于他们的 在临床试验中以及在体外、体外和 在艾伦·戴蒙德艾滋病中心作为单独项目进行的动物研究 研究中心和斯克里普斯研究所，我们将选择一个 用于阶段评估的2、3或4种试剂的最佳组合 在感染HIV-1的成人和儿童中进行I/II临床试验。如果 成功，那么在这个提议之后，最佳组合 将被带到大规模的关键临床试验中，以获得 产品的上市审批。