Study of TA-NIC to Assess the Efficacy and Safety of the Vaccine as an Aid to Smoking Cessation

NCT00633321 | Completed Phase 2

• 1 other identifier: TA-NIC/04
• Study Type: interventional
• Target: 522
• Locations: 1 country
• Sites: 9

Brief Summary

Over 1 billion people worldwide smoke, resulting in an estimated 4 million deaths annually from smoking-related disease.1 Persistent and long-term smoking leads to an increased risk of cardiovascular damage, respiratory disease, and a higher incidence of a variety of cancers; but for smokers who can quit there is an immediate and significant beneficial impact on their health and life expectancy. Cigarette smoking remains the leading preventable cause of death in the United States (US), accounting for approximately 1 of every 5 deaths (438,000 people) each year. This Phase 2 study will investigate the efficacy and tolerability of 2 doses of TA-NIC compared to placebo as an aid to smoking cessation in smokers who are motivated to quit.

Conditions

Smoking

Keywords

smoking cessation; quit smoking; smoking vaccine; nicotine vaccine; TA-NIC; Aid for smoking cessation in smokers motivated to quit

Outcome Measures

Primary Outcomes (1)

• 4-week assessment period quit rate at Week 26 measured by self-reported abstinence in the 4 weeks immediately prior to the 26 week visit and supported by CO breath test data

  Week 26

Secondary Outcomes (8)

• Measures of anti-nicotine antibody levels at key study visits

  Prospective

• Quit status at the final follow-up visit (Week 52)

  Week 52

• CO breath test measurements at key study visits

  Prospective

• Serum cotinine levels at key study visits

  Prospective

• Nicotine dependence as measured by Fagerström score, for those subjects who are still smokers

  Prospective

Study Arms (3)

1

EXPERIMENTAL

TA-NIC 100 μg

Biological: TA-NIC

2

EXPERIMENTAL

TA-NIC 250 μg

Biological: TA-NIC

3

PLACEBO COMPARATOR

Biological: Placebo

Interventions

TA-NIC BIOLOGICAL

TA-NIC vaccine will be administered to each subject as 7 single doses administered at Weeks 0, 2, 4, 6, 8, 12, and 16.

1; 2

Placebo BIOLOGICAL

Placebo will be administered to each subject as 7 single doses administered at Weeks 0, 2, 4, 6, 8, 12, and 16.

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years
• Female subjects must be either of non child bearing potential (i.e., either surgically sterilized or post menopausal) or must be using adequate contraception, have a negative pregnancy test and must agree to continue to use such precautions for 3 months after the last immunization. Acceptable contraceptive methods are oral or parenteral hormonal contraceptives; intrauterine device; barrier and spermicide. Abstinence or partner vasectomy are not acceptable methods.
• A "smoker" who has smoked on a regular basis for a least a year and is currently smoking at least 10 cigarettes per day
• Is motivated to quit smoking in the next 12 weeks
• Agrees to avoid smoking cessation pharmacotherapies, and any other methods of smoking cessation, other than those provided as part of this protocol
• Has good general health as determined by medical history, general clinical examination, vital signs (systolic blood pressure ≤140 mm Hg, diastolic blood pressure ≤90 mm Hg, heart rate ≤100 beats per minute, and body temperature of 36.1°-37.8° C), and clinical laboratory test results; and has a World Health Organization (WHO) performance status of 0 or 1 (see Appendix A for WHO performance status scale)
• Has provided written informed consent.

You may not qualify if:

• Have known immunodeficiency, or tested positive for human immunodeficiency virus (HIV) or hepatitis B at screening.
• Are taking medication known to have significant immunosuppressive effects such as systemic glucocorticoids (topical and inhaled formulations are permitted)
• Are intending to use other forms of smoking cessation pharmacotherapies or other methods of smoking cessation during the period of the study, other than those provided as part of this protocol; or who are receiving smoking cessation products (e.g., bupropion, clonidine, nortriptyline) for indications other than smoking cessation during the period of study
• History of sensitivity to aluminum hydroxide gel
• History of severe adverse reaction to cholera vaccine
• Known current user of drugs of abuse, or with a recent history (within the past 6 months) of use of drugs of abuse
• Recent (within the past 6 months) history of alcohol abuse
• Current non-cigarette tobacco use
• Previous vaccination with TA-NIC
• Participation in another clinical study within 30 days before study entry
• Female subjects with a positive pregnancy test; lactating mothers; women of child-bearing potential who do not agree to continue adequate contraception (i.e., oral or parenteral hormonal contraceptives, intrauterine device, barrier, and/or spermicide) and pregnancy tests from start of study through 3 months after the last immunization; or women who are planning to become pregnant during the period of the study
• Clinical laboratory value outside the normal range of the central laboratory (see Appendix G), unless the value has been justified by the Investigator in writing
• Any other factor that in the opinion of the Investigator would make the subject unsuitable for the study.

Sponsors & Collaborators

• Celtic Pharma Development Services: lead

Study Sites (9)

Benchmark Research

Sacramento, California, 95816, United States

Location

Benchmark Research

Metairie, Louisiana, 70006, United States

Location

Columbia Medical Practice

Columbia, Maryland, 21045, United States

Location

Centennial Medical Group

Elkridge, Maryland, 21075, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

CNS Research Institute, P.C.

Clementon, New Jersey, 08021, United States

Location

CRI Worldwide, LLC Kirkbride Center

Philadelphia, Pennsylvania, 19139, United States

Location

Benchmark Research

Austin, Texas, 78705, United States

Location

Benchmark Research - Fort Worth

Fort Worth, Texas, 76135, United States

Location

Related Publications (35)

• Doll R, Hill AB. The mortality of doctors in relation to their smoking habits: a preliminary report. 1954. BMJ. 2004 Jun 26;328(7455):1529-33; discussion 1533. doi: 10.1136/bmj.328.7455.1529. No abstract available.

  PMID: 15217868 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and economic costs--United States, 1995-1999. MMWR Morb Mortal Wkly Rep. 2002 Apr 12;51(14):300-3.

  PMID: 12002168 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 1997-2001. MMWR Morb Mortal Wkly Rep. 2005 Jul 1;54(25):625-8.

  PMID: 15988406 BACKGROUND

• Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2004;(3):CD000146. doi: 10.1002/14651858.CD000146.pub2.

  PMID: 15266423 BACKGROUND

• Hall SM, Humfleet GL, Reus VI, Munoz RF, Hartz DT, Maude-Griffin R. Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry. 2002 Oct;59(10):930-6. doi: 10.1001/archpsyc.59.10.930.

  PMID: 12365880 BACKGROUND

• Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000031. doi: 10.1002/14651858.CD000031.pub3.

  PMID: 17253443 BACKGROUND

• Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999 Mar 4;340(9):685-91. doi: 10.1056/NEJM199903043400903.

  PMID: 10053177 BACKGROUND

• Silagy C, Mant D, Fowler G, Lodge M. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet. 1994 Jan 15;343(8890):139-42. doi: 10.1016/s0140-6736(94)90933-4.

  PMID: 7904003 BACKGROUND

• West RJ, Russell MA. Cardiovascular and subjective effects of smoking before and after 24 h of abstinence from cigarettes. Psychopharmacology (Berl). 1987;92(1):118-21. doi: 10.1007/BF00215491.

  PMID: 3110822 BACKGROUND

• Pentel PR, Malin DH, Ennifar S, Hieda Y, Keyler DE, Lake JR, Milstein JR, Basham LE, Coy RT, Moon JW, Naso R, Fattom A. A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacol Biochem Behav. 2000 Jan 1;65(1):191-8. doi: 10.1016/s0091-3057(99)00206-3.

  PMID: 10638653 BACKGROUND

• Malin DH, Lake JR, Lin A, Saldana M, Balch L, Irvin ML, Chandrasekara H, Alvarado CL, Hieda Y, Keyler DE, Pentel PR, Ennifar S, Basham LE, Naso R, Fattom A. Passive immunization against nicotine prevents nicotine alleviation of nicotine abstinence syndrome. Pharmacol Biochem Behav. 2001 Jan;68(1):87-92. doi: 10.1016/s0091-3057(00)00436-6.

  PMID: 11274712 BACKGROUND

• Hieda Y, Keyler DE, VanDeVoort JT, Niedbala RS, Raphael DE, Ross CA, Pentel PR. Immunization of rats reduces nicotine distribution to brain. Psychopharmacology (Berl). 1999 Apr;143(2):150-7. doi: 10.1007/s002130050930.

  PMID: 10326777 BACKGROUND

• Hieda Y, Keyler DE, Ennifar S, Fattom A, Pentel PR. Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain. Int J Immunopharmacol. 2000 Oct;22(10):809-19. doi: 10.1016/s0192-0561(00)00042-4.

  PMID: 10963853 BACKGROUND

• Fagerstrom KO, Schneider NG. Measuring nicotine dependence: a review of the Fagerstrom Tolerance Questionnaire. J Behav Med. 1989 Apr;12(2):159-82. doi: 10.1007/BF00846549.

  PMID: 2668531 BACKGROUND

• Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111/j.1360-0443.1991.tb01879.x.

  PMID: 1932883 BACKGROUND

• Kozlowski LT, Porter CQ, Orleans CT, Pope MA, Heatherton T. Predicting smoking cessation with self-reported measures of nicotine dependence: FTQ, FTND, and HSI. Drug Alcohol Depend. 1994 Feb;34(3):211-6. doi: 10.1016/0376-8716(94)90158-9.

  PMID: 8033758 BACKGROUND

• Hurt RD, Sachs DP, Glover ED, Offord KP, Johnston JA, Dale LC, Khayrallah MA, Schroeder DR, Glover PN, Sullivan CR, Croghan IT, Sullivan PM. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997 Oct 23;337(17):1195-202. doi: 10.1056/NEJM199710233371703.

  PMID: 9337378 BACKGROUND

• Hays JT, Hurt RD, Rigotti NA, Niaura R, Gonzales D, Durcan MJ, Sachs DP, Wolter TD, Buist AS, Johnston JA, White JD. Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial. Ann Intern Med. 2001 Sep 18;135(6):423-33. doi: 10.7326/0003-4819-135-6-200109180-00011.

  PMID: 11560455 BACKGROUND

• Brauer LH, Behm FM, Lane JD, Westman EC, Perkins C, Rose JE. Individual differences in smoking reward from de-nicotinized cigarettes. Nicotine Tob Res. 2001 May;3(2):101-9. doi: 10.1080/14622200123249.

  PMID: 11403723 BACKGROUND

• Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV. Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Clin Pharmacol Ther. 1994 Jul;56(1):86-99. doi: 10.1038/clpt.1994.105.

  PMID: 8033499 BACKGROUND

• Rose JE, Behm FM, Westman EC. Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy. Exp Clin Psychopharmacol. 1998 Aug;6(3):331-43. doi: 10.1037//1064-1297.6.3.331.

  PMID: 9725117 BACKGROUND

• Cappelleri JC, Bushmakin AG, Baker CL, Merikle E, Olufade AO, Gilbert DG. Confirmatory factor analyses and reliability of the modified cigarette evaluation questionnaire. Addict Behav. 2007 May;32(5):912-23. doi: 10.1016/j.addbeh.2006.06.028. Epub 2006 Jul 27.

  PMID: 16875787 BACKGROUND

• Cox LS, Tiffany ST, Christen AG. Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res. 2001 Feb;3(1):7-16. doi: 10.1080/14622200020032051.

  PMID: 11260806 BACKGROUND

• World Health Organization; Tobacco Free Initiative: Why is tobacco a public health priority? http:www.who.int/tobacco/en

  BACKGROUND

• Fiore MC, Bailey WC, Cohen SJ, et al. Smoking cessation. Clinical Practice Guideline No 18. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, April 1996. (AHCPR Publication No 96-0692).

  BACKGROUND

• National Center for Health Statistics (US). Health, United States, 2004: With Chartbook on Trends in the Health of Americans. Hyattsville (MD): National Center for Health Statistics (US); 2004 Sep. Report No.: 2004-1232. Available from http://www.ncbi.nlm.nih.gov/books/NBK20751/

  PMID: 20698065 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Tobacco use among adults--United States, 2005. MMWR Morb Mortal Wkly Rep. 2006 Oct 27;55(42):1145-8.

  PMID: 17065979 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults--United States, 1994. MMWR Morb Mortal Wkly Rep. 1996 Jul 12;45(27):588-90.

  PMID: 9132579 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults--United States, 2000. MMWR Morb Mortal Wkly Rep. 2002 Jul 26;51(29):642-5.

  PMID: 12186222 BACKGROUND

• CDC. The Health Consequences of Smoking: Nicotine Addiction: A Report of the Surgeon General 1988. Rockville, MD: U.S. Department of Health and Human Services, CDC, Center for Health Promotion and Education, Office on Smoking and Health; 1988.

  BACKGROUND

• CDC. Reducing Tobacco Use: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, CDC, Office on Smoking and Health; 2000.

  BACKGROUND

• Fiore MC, Bailey WC, Cohen SJ, Dorfman SF, Goldstein MG, Gritz ER, et al. Treating Tobacco Use and Dependence: Quick Reference Guide for Clinicians. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service; 2000.

  BACKGROUND

• USDHHS. The health consequences of smoking: nicotine addiction. Rockville, Maryland: Office on Smoking and Health, 1988.

  BACKGROUND

• Westman, E. C., Levin, E. D., & Rose, J. E. Smoking while wearing the nicotine patch: Is smoking satisfying or harmful? Clinical Research. 1992;40, 871A.

  BACKGROUND

• Cappelleri JC, Bushmakin AG, Baker CL, Merikle E, Olufade AO, Gilbert DG. Confirmatory validation of the Brief Questionnaire of Smoking Urges. Value in Health 2005;8(3):334.

  BACKGROUND

MeSH Terms

Conditions

Smoking; Smoking Cessation

Interventions

TA-NIC

Condition Hierarchy (Ancestors)

Behavior; Health Behavior

Study Officials

• Krefetz

  CNS Research Institute, P.C

  PRINCIPAL INVESTIGATOR

• Gruener

  CRI Worldwide, LLC

  PRINCIPAL INVESTIGATOR

• Coats

  Benchmark Research

  PRINCIPAL INVESTIGATOR

• Rarick

  Benchmark Research

  PRINCIPAL INVESTIGATOR

• Seger

  Benchmark Research - Fort Worth

  PRINCIPAL INVESTIGATOR

• Jeanfreau

  Benchmark Research

  PRINCIPAL INVESTIGATOR

• Geller

  Centennial Medical Group

  PRINCIPAL INVESTIGATOR

• Saway

  Columbia Medical Practice

  PRINCIPAL INVESTIGATOR

• Dale

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 5, 2008
• First Posted: March 12, 2008
• Study Start: May 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: February 1, 2009
• Last Updated: June 8, 2011

Record last verified: 2011-06

Locations

US (9)