CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS

CD4 IGG2 和 HUMAB 组合的临床试验

• 批准号: 6373836
• 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/6373836
• 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 HIV-1 感染是一个主要目标。 领先候选人 免疫疗法包括广泛中和的人单克隆抗体 抗体 (HuMAb) IgG1b12，连接到 gp120、2F5 上的 CD4 结合位点 gp41 上的保守表位和 2g12 上的不连续区域 GP120。 此外，CD4-IgG2 表现出有效且广泛的中和作用 HIV-1，包括初级分离株。 它是第三代CD4- 含有两条 CD4-人 IgG2 重链的分子 融合蛋白和 CD4-人 kappa 轻链融合的两条链 蛋白质。 而 IgG1b12、2F5、2G12 和 CD4-IgG2 表现出显着的中和作用 作为单一代理人的活动，发展有效的被动 免疫疗法可能需要使用其中两种或多种的混合物 代理。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团体组成的联盟，开发了这些 试剂（IgG1b12 - Dennis Burton 博士；2F5 和 2G12 - Hermann 博士 卡廷格；和，CD4-IgG2 - 博士。格雷厄姆·阿拉维和保罗·马登) 协调和加速单一药物的临床试验 代理的组合。 该提案的目标是制造， 准备新药研究申请并获得监管 美国食品药品监督管理局批准临床研究 给药并进行药物临床试验以评估 HIV-1 感染者的耐受性、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 1997-98 年在 国家过敏和传染病研究所。 基于他们的 临床试验以及体外、离体和 亚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 种药物的最佳组合 HIV-1 感染成人和儿童的 I/II 临床试验。 如果 成功的话，那么在这个提议之后，最优的组合 将进行大规模的关键临床试验，以获得 产品的营销批准。