Efficacy of NicVAX in Smokers Who Want to Quit Smoking

• Continuous smoking abstinence [ Time Frame: 8 week interval (Weeks 19 to 26, inclusive, following the first vaccination) ] [ Designated as safety issue: No ]
  

• Point prevalence abstinence [ Time Frame: at 12 months, and other time points; extended up to 24 months ] [ Designated as safety issue: No ]
  
• Duration of smoking abstinence [ Time Frame: at 6 and 12 months ] [ Designated as safety issue: No ]
  
• Safety [ Time Frame: 0-12 months, and extended up to 24 months ] [ Designated as safety issue: Yes ]
  
• Numbers of cigarettes per day [ Time Frame: Target quit day to 12 months ] [ Designated as safety issue: No ]
  
• Cumulative number of cigarettes smoked [ Time Frame: during weeks 18-26 ] [ Designated as safety issue: No ]
  
• Exhaled CO [ Time Frame: at clinic visits ] [ Designated as safety issue: No ]
  
• Urine cotinine [ Time Frame: at clinic visits ] [ Designated as safety issue: No ]
  
• Modified Minnesota Nicotine Withdrawal Questionnaire [ Time Frame: weekly for 6 months, daily for 14 days after quit attempt ] [ Designated as safety issue: Yes ]
  
• Cigarette Evaluation Questionnaire (a.k.a. Nabi Questionnaire) [ Time Frame: weekly for 6 motnhs ] [ Designated as safety issue: Yes ]
  
• Fagerstrom Test for Nicotine Dependence [ Time Frame: baseline, weeks 26 and 52 ] [ Designated as safety issue: No ]
  
• serum anti-nicotine antibody concentrations by Elisa [ Time Frame: periodic from baseline to month 12, extended to month 24 ] [ Designated as safety issue: No ]
  

Cigarette smoking is responsible for over 400,000 (1 out of every 5) deaths in the United States each year. Most smokers are aware of the health consequences and want to quit, but have difficulty doing so. Only 3-5% of smokers who quit on their own are successful. Since the vast majority of those who attempt to quit will fail, the need for better approaches to smoking cessation is clear and urgent. A safe and effective means of blocking the effects of nicotine would be of considerable interest as a potential treatment for tobacco use. Vaccination to produce nicotine-specific antibodies may be viewed as an alternative method of blocking nicotine effects. Nicotine is a small molecule that does not elicit an immune response in animals of humans. In order for the immune system to respond to this hapten, nicotine can be combined or bound to a larger molecule in a unique manner so that an immune response is mounted against nicotine. Nabi Biopharmaceuticals has developed a conjugate vaccine (NicVAX) that consists of 3'-aminomethylnicotine bound to Pseudomonas aeruginosa exoprotein A, an exotoxin that has been made non-toxic by an amino acid deletion. Subjects will be randomized to one of four treatment groups.

Within each treatment group, 75 subjects will be randomized in a 2:1 ratio (NicVAX:Placebo), yielding a total of 50 active and 25 placebo subjects for each treatment group. There will be 12 subjects enrolled in a fifth open label arm to evaluate immunogenicity. A quit date will be set at the end of week 7 or at the end of week 5, depending on the dosing schedule. Continuous abstinence will be measured between the end of week 18 and the end of week 26.