PHASE 1 STUDY OF SAFETY & IMMUNOGENICITY OF AN ALUM-FORMULATED RECOMBINANT RICIN

第一阶段安全性研究

• 批准号: 7623849
• 负责人: ELLEN S VITETTA
• 金额: $ 31.19万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623849
• 关键词: PHASE; STUDY; SAFETY; IMMUNOGENICITY; ALUM; PHASE; STUDY; SAFETY; IMMUNOGENICITY; ALUM

DESCRIPTION (provided by applicant): Ricin is a highly potent toxin, easily produced from abundantly available castor beans, for which there is no vaccine to protect against intoxication or effective post-exposure treatment beyond supportive care. This has led the Centers for Disease Control and Prevention to classify ricin as a level B biothreat. Indeed, evidence has been found suggesting that terrorist groups have attempted to develop it as a weapon, and there have been instances of domestic attacks. The investigators have developed a non-toxic ricin vaccine, RiVax, from the A-chain subunit of ricin, by introducing two site-specific mutations that eliminate both its ribotoxic and vascular leak syndrome-inducing activities. Once preclinical testing demonstrated that this vaccine, as a frozen sucrose/Tween formulation, was safe and immunogenic in mice and rabbits, the investigators conducted a Phase 1 study in 15 human volunteers and showed that it was safe and able to elicit ricin neutralizing immune responses. In order to improve the efficacy of this vaccine, by increasing the degree and duration of the response, the investigators have developed an aluminum hydroxide (Alhydrogel) formulation and have shown that it greatly improves immunogenicity in mice. The investigators now propose to conduct a dose-escalating Phase 1 trial, involving 3 groups of 10 healthy volunteers to determine if this new formulation is safe in humans and increases and prolongs the response. Doses of 1, 10 and 100 micrograms - each with 0.5 mg Alhydrogel, will be given at weeks 0, 6, and 26 and serum will be assessed for anti-vaccine and neutralizing titers.

描述（由申请人提供）： Ricin是一种高度有效的毒素，很容易由大量可用的蓖麻豆产生，为此，没有疫苗可以防止中毒或有效的后暴露后治疗。 这导致了疾病控制和预防中心将赖克蛋白分类为B级Biothreat。 确实，已经发现有证据表明恐怖组织试图将其发展为武器，并且发生了国内攻击的情况。 研究人员通过引入两个特异性突变，从而消除了其核糖毒性和血管泄漏综合征的活性，从而从Ricin的A链亚基中开发了一种无毒的Ricin疫苗Rivax。 一旦临床前测试表明，作为一种冷冻的蔗糖/补间配方，这种疫苗在小鼠和兔子中是安全且免疫原性的，研究人员在15名人类志愿者中进行了1期研究，并表明它是安全的，并且能够引起ricin中和中和免疫反应。 为了通过提高反应的程度和持续时间来提高该疫苗的疗效，研究人员开发了氢氧化铝（Alhydrogel）制剂，并表明它极大地改善了小鼠的免疫原性。 研究人员现在建议进行剂量提升的第1阶段试验，涉及3组10名健康志愿者，以确定这种新的配方在人类中是否安全，并增加并延长了反应。 1、10和100微克的剂量将在第0、6和26周给予0.5 mg Alhydrogel，并将评估血清的抗疫苗和中和滴度。