Clinical trial NCT00318383: Efficacy of NicVAX in Smokers Who Want to Quit Smoking
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smoking Cessation
Keywords: Vaccine
Immunogenicity
Randomized Controlled Trial
Lead sponsor: National Institute on Drug Abuse (NIDA)
Sponsor class: NIH
Collaborators: name: Nabi Biopharmaceuticals
First posted: 2006-04-26
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Continuous smoking abstinence
timeFrame: 8 week interval (Weeks 19 to 26, inclusive, following the first vaccination)
Secondary outcomes:
measure: Point prevalence abstinence
timeFrame: at 12 months, and other time points; extended up to 24 months
measure: Duration of smoking abstinence
timeFrame: at 6 and 12 months
measure: Safety
timeFrame: 0-12 months, and extended up to 24 months
measure: Numbers of cigarettes per day
timeFrame: Target quit day to 12 months
measure: Cumulative number of cigarettes smoked
timeFrame: during weeks 18-26
measure: Exhaled CO
timeFrame: at clinic visits
measure: Urine cotinine
timeFrame: at clinic visits
measure: Modified Minnesota Nicotine Withdrawal Questionnaire
timeFrame: weekly for 6 months, daily for 14 days after quit attempt
measure: Cigarette Evaluation Questionnaire (a.k.a. Nabi Questionnaire)
timeFrame: weekly for 6 motnhs
measure: Fagerstrom Test for Nicotine Dependence
timeFrame: baseline, weeks 26 and 52
measure: serum anti-nicotine antibody concentrations by Elisa
timeFrame: periodic from baseline to month 12, extended to month 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: College Park
country: United States
facility: Department of Public & Community Health
state: Maryland
city: Boston
country: United States
facility: Tobacco Research Center, Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Nabi Biopharmaceuticals
name: Matt Hohenboken, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Fahim RE, Kessler PD, Fuller SA, Kalnik MW. Nicotine vaccines. CNS Neurol Disord Drug Targets. 2011 Dec;10(8):905-15. doi: 10.2174/187152711799219343.
citation: Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA, Tashkin DP, Reus VI, Akhavain RC, Fahim RE, Kessler PD, Niknian M, Kalnik MW, Rennard SI. Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic. Clin Pharmacol Ther. 2011 Mar;89(3):392-9. doi: 10.1038/clpt.2010.317. Epub 2011 Jan 26.