Efficacy of NicVAX in Smokers Who Want to Quit Smoking

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.

Inclusion Criteria:

- Smokes at least 15 cigarettes per day

- Wants to quit smoking

- Good general health

- Negative pregnancy test prior to study entry

- Carbon monoxide level greater than 10 ppm

Exclusion Criteria:

- Prior exposure to NicVAX or any other nicotine vaccine

- Known allergic reaction to alum or any of the components of the vaccine

- Use of steroids, immunosuppressive agents or other medication that might interfere
with an immune response