Efficacy of NicVAX in Smokers Who Want to Quit Smoking

Smoking Cessation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00318383
• Other study ID #: Nabi - 4512
• Secondary ID: 1R01DA017894-01A
• Status: Completed
• Phase: Phase 2
• First received: April 24, 2006
• Last updated: January 11, 2017
• Start date: May 2006
• Est. completion date: December 2007

Study information

• Verified date: November 2008
• Source: National Institute on Drug Abuse (NIDA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: December 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

Biological:
• NicVAX conjugate vaccine
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
• Placebo
Phosphate buffered saline and ALhydrogel of identical appearance to NicVAX; IM in 4 or 5 doses over 6 months

Locations

Country	Name	City	State
United States	Tobacco Research Center, Massachusetts General Hospital	Boston	Massachusetts
United States	Department of Public & Community Health	College Park	Maryland
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
National Institute on Drug Abuse (NIDA)	Nabi Biopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Continuous smoking abstinence		8 week interval (Weeks 19 to 26, inclusive, following the first vaccination)	No
Secondary	Point prevalence abstinence		at 12 months, and other time points; extended up to 24 months	No
Secondary	Duration of smoking abstinence		at 6 and 12 months	No
Secondary	Safety		0-12 months, and extended up to 24 months	Yes
Secondary	Numbers of cigarettes per day		Target quit day to 12 months	No
Secondary	Cumulative number of cigarettes smoked		during weeks 18-26	No
Secondary	Exhaled CO		at clinic visits	No
Secondary	Urine cotinine		at clinic visits	No
Secondary	Modified Minnesota Nicotine Withdrawal Questionnaire		weekly for 6 months, daily for 14 days after quit attempt	Yes
Secondary	Cigarette Evaluation Questionnaire (a.k.a. Nabi Questionnaire)		weekly for 6 motnhs	Yes
Secondary	Fagerstrom Test for Nicotine Dependence		baseline, weeks 26 and 52	No
Secondary	serum anti-nicotine antibody concentrations by Elisa		periodic from baseline to month 12, extended to month 24	No