Efficacy of NicVAX in Smokers Who Want to Quit Smoking

Study Overview
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Brief Summary
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The purpose of this study is to determine whether vaccination with NicVAX will result in a higher continuous abstinence rate than vaccination with placebo in smokers who want to quit smoking. In addition, two different formulations and dosing schedules will be studied, to select the dose and dosing schedule which generates the highest level of anti-nicotine antibodies. The primary study period is 12 months, which was extended by amendment to include up to 2 years of observations.

Detailed Description
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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.

Official Title
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A Phase 2, Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Assess Efficacy of 3'-Aminomethylnicotine-P.Aeruginosa r-Exoprotein A Conjugate Vaccine (NicVAX) in Smokers Who Want to Quit Smoking

Conditions
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Smoking Cessation

Intervention / Treatment
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* Biological: NicVAX conjugate vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>200 mcg NicVAX in each of 4 doses | Biological: NicVAX conjugate vaccine<br>* 200 mcg or 400 mcg IM in 4 doses over 6 months; 200 mcg or 400 mcg IM in 5 doses over 6 months; 200 mcg (formulation 2) IM in 5 doses over 6 months; All are adsorbed onto Alhydrogel<br>* Other names: 3'-aminomethylnicotine-rEPA conjugate vaccine;|
| Experimental: 2<br>200 mcg NicVAX in each of 5 doses | Biological: NicVAX conjugate vaccine<br>* 200 mcg or 400 mcg IM in 4 doses over 6 months; 200 mcg or 400 mcg IM in 5 doses over 6 months; 200 mcg (formulation 2) IM in 5 doses over 6 months; All are adsorbed onto Alhydrogel<br>* Other names: 3'-aminomethylnicotine-rEPA conjugate vaccine;|
| Experimental: 3<br>400 mcg NicVAX in each of 4 doses | Biological: NicVAX conjugate vaccine<br>* 200 mcg or 400 mcg IM in 4 doses over 6 months; 200 mcg or 400 mcg IM in 5 doses over 6 months; 200 mcg (formulation 2) IM in 5 doses over 6 months; All are adsorbed onto Alhydrogel<br>* Other names: 3'-aminomethylnicotine-rEPA conjugate vaccine;|
| Experimental: 4<br>400 mcg NicVAX in each of 5 doses | Biological: NicVAX conjugate vaccine<br>* 200 mcg or 400 mcg IM in 4 doses over 6 months; 200 mcg or 400 mcg IM in 5 doses over 6 months; 200 mcg (formulation 2) IM in 5 doses over 6 months; All are adsorbed onto Alhydrogel<br>* Other names: 3'-aminomethylnicotine-rEPA conjugate vaccine;|
| Placebo Comparator: 5<br>Placebo in 4 or 5 doses | Biological: Placebo<br>* Phosphate buffered saline and ALhydrogel of identical appearance to NicVAX; IM in 4 or 5 doses over 6 months<br>|
| Experimental: 6<br>200 mcg NicVAX formulation 2 in each of 5 doses | Biological: NicVAX conjugate vaccine<br>* 200 mcg or 400 mcg IM in 4 doses over 6 months; 200 mcg or 400 mcg IM in 5 doses over 6 months; 200 mcg (formulation 2) IM in 5 doses over 6 months; All are adsorbed onto Alhydrogel<br>* Other names: 3'-aminomethylnicotine-rEPA conjugate vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous smoking abstinence |  | 8 week interval (Weeks 19 to 26, inclusive, following the first vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point prevalence abstinence |  | at 12 months, and other time points; extended up to 24 months | 
| Duration of smoking abstinence |  | at 6 and 12 months | 
| Safety |  | 0-12 months, and extended up to 24 months | 
| Numbers of cigarettes per day |  | Target quit day to 12 months | 
| Cumulative number of cigarettes smoked |  | during weeks 18-26 | 
| Exhaled CO |  | at clinic visits | 
| Urine cotinine |  | at clinic visits | 
| Modified Minnesota Nicotine Withdrawal Questionnaire |  | weekly for 6 months, daily for 14 days after quit attempt | 
| Cigarette Evaluation Questionnaire (a.k.a. Nabi Questionnaire) |  | weekly for 6 motnhs | 
| Fagerstrom Test for Nicotine Dependence |  | baseline, weeks 26 and 52 | 
| serum anti-nicotine antibody concentrations by Elisa |  | periodic from baseline to month 12, extended to month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Immunogenicity, Randomized Controlled Trial