Efficacy of NicVAX in Smokers Who Want to Quit Smoking

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

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Biological: NicVAX conjugate vaccine; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 313
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • San Francisco, California, United States, 94143
      • University of California
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
  • Maryland
    • College Park, Maryland, United States, 20742
      • Department of Public & Community Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Tobacco Research Center, Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Wisconsin
    • Madison, Wisconsin, United States, 53711
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 200 mcg NicVAX in each of 4 doses	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; Other Names: 3'-aminomethylnicotine-rEPA conjugate vaccine
Experimental: 2; 200 mcg NicVAX in each of 5 doses	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; Other Names: 3'-aminomethylnicotine-rEPA conjugate vaccine
Experimental: 3; 400 mcg NicVAX in each of 4 doses	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; Other Names: 3'-aminomethylnicotine-rEPA conjugate vaccine
Experimental: 4; 400 mcg NicVAX in each of 5 doses	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; Other Names: 3'-aminomethylnicotine-rEPA conjugate vaccine
Placebo Comparator: 5; Placebo in 4 or 5 doses	Biological: Placebo; Phosphate buffered saline and ALhydrogel of identical appearance to NicVAX; IM in 4 or 5 doses over 6 months
Experimental: 6; 200 mcg NicVAX formulation 2 in each of 5 doses	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; Other Names: 3'-aminomethylnicotine-rEPA conjugate vaccine

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Collaborators: Nabi Biopharmaceuticals

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: April 24, 2006
• First Submitted That Met QC Criteria: April 24, 2006
• First Posted (Estimate): April 26, 2006

Study Record Updates

• Last Update Posted (Estimate): January 12, 2017
• Last Update Submitted That Met QC Criteria: January 11, 2017
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Vaccine; Immunogenicity; Randomized Controlled Trial
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: Nabi - 4512; 1R01DA017894-01A1 (U.S. NIH Grant/Contract)