Efficacy of a Nicotine Vaccine for Smoking Cessation

尼古丁疫苗戒烟的功效

• 批准号: 6867902
• 负责人: Arjen De Vos
• 金额: $ 258.88万
• 依托单位: NABI BIOPHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6867902
• 关键词: clinical research; clinical trial phase II; drug abuse therapy; drug screening /evaluation; enzyme linked immunosorbent assay; human subject; human therapy evaluation; immunotherapy; nicotine; patient oriented research; pharmacokinetics; smoking cessation; substance abuse related behavior; vaccine evaluation

DESCRIPTION (provided by applicant): Tobacco use is the single leading preventable cause of death in the United States. Nicotine is an alkaloid derived from the tobacco plant that is primarily responsible for smoking's psychoactive and addictive effects. Immunotherapy may potentially be useful to prevent and/or treat addiction to nicotine and other drugs of abuse. Nicotine-specific antibodies would bind and sequester nicotine in the serum, thus preventing nicotine from reaching the brain as antibodies are too large to cross the blood brain barrier. Haptens, such as nicotine, can be made immunogenic by conjugation to carrier proteins to make nicotine vaccines. A number of studies have shown that, in animals, nicotine vaccines reduce the distribution of nicotine to the brain, attenuate the locomotor and stimulus properties of nicotine and prevent nicotine from relieving nicotine abstinence syndrome. In humans, such a vaccine may be an effective aid in smoking cessation and reduce the rate/time to relapse. Nabi has completed two studies of its proprietary nicotine vaccine NicVAXTM; one Phase 1 clinical trial (Nabi 4502) to evaluate safety in non-smoking adults, and one Phase 1/2 clinical trial in 21 smokers and 9 exsmokers (Nabi 4503). We have fully enrolled a multi-site, NIDA-funded Phase 2 clinical trial in 63 smokers (Nabi 4504). An additional Phase 2 clinical trial (Nabi 4505) in 30 smokers designed to compare 3 dosing schedules will be started in April, 2004. These trials are described more fully below. The results from these studies will form the basis for the additional efficacy and safety studies proposed in this application. The specific aim of this proposal is to demonstrate in a proof of concept, Phase 2, clinical trial of NicVAX in smokers (Nabi 4506) both the efficacy as measured by smoking cessation rates and the safety of the vaccine. Prior to initiating Nabi 4506 a new lot of NicVAX will be manufactured and tested for safety and immunogenicity in Nabi 45SI.

描述（由申请人提供）：烟草使用是美国单一的可预防死亡原因。尼古丁是一种源自烟草植物的生物碱，主要负责吸烟的精神活性和上瘾的作用。免疫疗法可能有助于预防和/或治疗对尼古丁和其他滥用药物的成瘾。尼古丁特异性抗体会结合并隔离血清中的尼古丁，从而防止尼古丁到达大脑，因为抗体太大而无法越过血脑屏障。可以通过与载体蛋白结合以生产尼古丁疫苗来使触觉（例如尼古丁）成为免疫原性。许多研究表明，在动物中，尼古丁疫苗减少了尼古丁对大脑的分布，减轻尼古丁的运动和刺激特性，并防止尼古丁缓解尼古丁的屈服综合征。在人类中，这种疫苗可能有效地戒烟，并降低复发的速度/时间。 NABI已经完成了两项有关其专有尼古丁疫苗NICVAXTM的研究；一阶段1临床试验（NABI 4502）评估非吸烟成年人的安全性，以及一项在21名吸烟者和9名Exsmokers（Nabi 4503）中进行的1/2期临床试验。我们已经在63名吸烟者（NABI 4504）中完全招募了一项由NIDA资助的2期临床试验。旨在比较3个剂量时间表的30种吸烟者中的另外2期临床试验（NABI 4505）将于2004年4月开始。这些试验在下面更全面地描述。这些研究的结果将构成本应用中提出的其他功效和安全研究的基础。 该提案的具体目的是在概念证明中证明，第2阶段，NICVAX在吸烟者中的临床试验（NABI 4506）都通过吸烟率和疫苗的安全性来衡量的疗效。在启动NABI 4506之前，将在NABI 45SI中生产和测试新的NICVAX的安全性和免疫原性。