Study of TA-NIC to Assess the Efficacy and Safety of the Vaccine as an Aid to Smoking Cessation

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose-Ranging Study of 100 or 250 μg of TA-NIC to Assess the Efficacy and Safety of the Vaccine as an Aid to Smoking Cessation

Over 1 billion people worldwide smoke, resulting in an estimated 4 million deaths annually from smoking-related disease.1 Persistent and long-term smoking leads to an increased risk of cardiovascular damage, respiratory disease, and a higher incidence of a variety of cancers; but for smokers who can quit there is an immediate and significant beneficial impact on their health and life expectancy. Cigarette smoking remains the leading preventable cause of death in the United States (US), accounting for approximately 1 of every 5 deaths (438,000 people) each year.

This Phase 2 study will investigate the efficacy and tolerability of 2 doses of TA-NIC compared to placebo as an aid to smoking cessation in smokers who are motivated to quit.

This is a multicenter, double-blind, randomized, placebocontrolled, 3-arm, Phase 2 study evaluating the efficacy and safety of TA-NIC as an aid for smoking cessation in smokers motivated to quit within 12 weeks. At the start of the study, each subject will set a Target Quit Date, which must be within 12 weeks after first injection. Each subject will receive 7 injections (vaccinations) from Weeks 0 to 16. Subjects will be encouraged to follow a phased reduction in cigarette consumption leading up to the Target Quit Date. All vaccinated subjects will be offered a counseling session at each clinic visit and will be contacted by telephone at Weeks 1, 3, 5, 7, 9, 14, 18, and 21 to provide up to 10 minutes of support and counseling for their smoking cessation. Smoking cessation will be measured during a 4-week assessment period from Week 22 to Week 26. Smoking cessation will be defined as complete abstinence during this 4-week period. Subject follow-up will continue to Week 52.

Inclusion Criteria:

• Aged ≥18 years
• Female subjects must be either of non child bearing potential (i.e., either surgically sterilized or post menopausal) or must be using adequate contraception, have a negative pregnancy test and must agree to continue to use such precautions for 3 months after the last immunization. Acceptable contraceptive methods are oral or parenteral hormonal contraceptives; intrauterine device; barrier and spermicide. Abstinence or partner vasectomy are not acceptable methods.
• A "smoker" who has smoked on a regular basis for a least a year and is currently smoking at least 10 cigarettes per day
• Is motivated to quit smoking in the next 12 weeks
• Agrees to avoid smoking cessation pharmacotherapies, and any other methods of smoking cessation, other than those provided as part of this protocol
• Has good general health as determined by medical history, general clinical examination, vital signs (systolic blood pressure ≤140 mm Hg, diastolic blood pressure ≤90 mm Hg, heart rate ≤100 beats per minute, and body temperature of 36.1°-37.8° C), and clinical laboratory test results; and has a World Health Organization (WHO) performance status of 0 or 1 (see Appendix A for WHO performance status scale)
• Has provided written informed consent.

Exclusion Criteria:

• Have known immunodeficiency, or tested positive for human immunodeficiency virus (HIV) or hepatitis B at screening.
• Are taking medication known to have significant immunosuppressive effects such as systemic glucocorticoids (topical and inhaled formulations are permitted)
• Are intending to use other forms of smoking cessation pharmacotherapies or other methods of smoking cessation during the period of the study, other than those provided as part of this protocol; or who are receiving smoking cessation products (e.g., bupropion, clonidine, nortriptyline) for indications other than smoking cessation during the period of study
• History of sensitivity to aluminum hydroxide gel
• History of severe adverse reaction to cholera vaccine
• Known current user of drugs of abuse, or with a recent history (within the past 6 months) of use of drugs of abuse
• Recent (within the past 6 months) history of alcohol abuse
• Current non-cigarette tobacco use
• Previous vaccination with TA-NIC
• Participation in another clinical study within 30 days before study entry
• Female subjects with a positive pregnancy test; lactating mothers; women of child-bearing potential who do not agree to continue adequate contraception (i.e., oral or parenteral hormonal contraceptives, intrauterine device, barrier, and/or spermicide) and pregnancy tests from start of study through 3 months after the last immunization; or women who are planning to become pregnant during the period of the study
• Clinical laboratory value outside the normal range of the central laboratory (see Appendix G), unless the value has been justified by the Investigator in writing
• Any other factor that in the opinion of the Investigator would make the subject unsuitable for the study.