Improving the Efficacy of Anti-Nicotine Immunotherapy (PETNic002)

• Binding properties of vaccination-induced anti-nicotine antibodies [ Time Frame: Two weeks after last vaccination ] [ Designated as safety issue: No ]
• Side effects of vaccination [ Time Frame: After first vaccination until study completion ] [ Designated as safety issue: Yes ]
• Efficacy of vaccine for smoking cessation [ Time Frame: One, two and six months after quit day ] [ Designated as safety issue: No ]

The purpose of this study is to find out how vaccine-induced antibodies change the way the body processes nicotine from cigarettes. These antibodies absorb nicotine and can reduce nicotine levels in the brain. In this way, the vaccination may help to quit smoking. The central hypothesis is that anti-nicotine antibodies change kinetics of brain nicotine accumulation and distribution of nicotine between the brain and other body tissues. This vaccine is investigational which means that it is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA) to help people quit smoking.

• Biological: NIC002 in Aluminum hydroxide (Alum)
  Fifty-five subjects will receive 4 subcutaneous injections of 0.1 mg Nicotine-QB (NIC002) in Alum vaccine with a 4-week interval between injections.
  Other Names:

  • CYT002-NicQb (Nicotine-Qbeta)
  • Anti-Nicotine Vaccine
• Biological: Placebo Vaccine - Aluminum hydroxide
  Ten subjects will receive 4 subcutaneous injections of indistinguishable placebo (Alum alone) with a 4-week interval between injections.

• Experimental: NIC002 Vaccine in Aluminum hydroxide
  Intervention: Biological: NIC002 in Aluminum hydroxide (Alum)
• Placebo Comparator: Placebo Vaccine - Aluminum hydroxide
  Intervention: Biological: Placebo Vaccine - Aluminum hydroxide

Inclusion Criteria:

• 18-55 years old
• Smoked an average of at least 10 cigarettes per day for the past year
• Have an expired air Carbon Monoxide (CO) reading of at least 15 ppm
• Express a desire to quit smoking in the next three to four months.
• Potential subjects must agree to use acceptable contraception during their participation in this study.
• Potential subjects must agree to avoid the following during their participation in this study:
• participation in any other nicotine-related modification strategy outside of this protocol

• use of tobacco products other than cigarettes, including pipe tobacco, cigars, snuff, and chewing tobacco

  • use of experimental (investigational) drugs or devices;
  • use of illegal drugs;
  • use of psychiatric medications;
  • use of opiate medications;
  • use of systemic steroids or other immunosuppressive agents.

Exclusion Criteria:

1. Hypertension (systolic >140 mm Hg, diastolic >100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
2. Hypotension with symptoms (systolic <90 mm Hg, diastolic <60 mm Hg).
3. Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety.
4. Coronary heart disease or other cardiovascular disorder;
5. Lifetime history of heart attack;
6. Cardiac rhythm disorder (irregular heart rhythm);
7. Chest pains (unless history, exam, and Electrocardiogram (ECG) clearly indicate a non-cardiac source);
8. Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
9. Liver or kidney disorder (except kidney stones, gallstones);
10. Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
11. Active ulcers in the past 30 days;
12. Lung disorder (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
13. Brain abnormality or other neurological disorder (including but not limited to stroke, brain tumor, and seizure disorder);
14. Recent, unexplained fainting spells;
15. Problems giving blood samples;
16. Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
17. Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
18. Skin disorder;
19. Autoimmune disease;
20. Human immunodeficiency virus (HIV) or HIV risk behavior;
21. Severe allergies;
22. Other major medical condition;
23. Current psychiatric disease including major depressive episode, panic attack, psychosis, bipolar disorder or eating disorder;
24. Pregnant or nursing mothers;

25. Use (within the past 30 days) of:

    • Illegal drugs (or if the urine drug screen is positive),
    • Experimental (investigational) drugs;
    • Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
    • Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed)
    • Smokeless tobacco (chewing tobacco, snuff), cigars, pipes or e-cigarettes;
    • Nicotine replacement therapy or any other smoking cessation aid.
26. Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire will be used to assess alcohol abuse.
27. Previous history of negative experiences with "flu" vaccine or any other vaccine.
28. High chronic exposure to aluminum (occupational or medical);
29. Pulmonary function test results < 60% of predicted value for FEV1 and FVC;
30. Body Mass Index > 38kg/m2;
31. History of psychosis or bipolar disorder;
32. Prior exposure to CTY002- NicQ or any other nicotine vaccine.

• National Institute on Drug Abuse (NIDA)
• Wake Forest University
• Novartis